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Multifaceted Role of Induced Pluripotent Stem Cells in Preclinical Cardiac Regeneration Research

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Handbook of Stem Cell Applications

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Abstract

The increasing rate of cardiovascular disease (CVD) worldwide contributes to a worsening quality of life in surviving patients and a socioeconomic burden on the health care system. There is currently no cure for CVD. The innovation of novel cardiovascular therapies has traditionally been significantly stalled due to several obstacles, such as complications resulting from scar tissue formation and the need for a representative and patient-specific cardiac disease model. However, the last two decades have seen the emergence of induced pluripotent stem cells (iPSCs), which have risen at the forefront of regenerative medicine research as a novel patient-specific stem cell source. In this chapter, we will cover the basics of cell reprogramming, iPSC generation, and quality assessment before moving on to the versatile array of roles that iPSCs hold. We will outline three potential uses of iPSCs in heart regeneration research: as a precursor for patient-specific cells as an in vitro model, as cells for in vivo implantation purposes, and as a source of the secretome. Finally, we aim to highlight the importance of incorporating patient-specific biological characteristics within large-scale research and identify the gaps in the applications of iPSCs in cardiac regenerative medicine.

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Abbreviations

A2M :

Alpha-2-macroglobulin

AP:

Alkaline phosphatase

APOE:

Apolipoprotein A

ARV C/D:

Arrhythmogenic right ventricular cardiomyopathy/dysplasia

ATF4:

Activating transcription factor 4

BMP4:

Bone morphogenetic protein 4

CAV1/2:

Caveolin 1/2

CLDN6:

Claudin 6

c-Myc :

Cellular-myelocytomatosis

CNMD or LECT1:

Chondromodulin

CNN1:

Calponin 1

COL1A1:

Collagen type I or II alpha 1 chain

CVD :

Cardiovascular disease

Cx43:

Connexin 43

CXCR4:

C-X-C chemokine receptor type 4

DDR2:

Discoidin domain receptor tyrosine kinase 2

DKKI:

Dickkopf-related protein 1

EHT:

Engineered heart tissue

ERR :

Estrogen-related receptor

ESCs:

Embryonic stem cells

ESRG :

ESC related

EV:

Extracellular vesicle

FACS:

Fluorescence-activated cell sorting

FBS:

Fetal bovine serum

FGF2:

Fibroblast growth factor 2

FHL ½:

Four-and-a-half Lin11, Isl-1 and Mec-3 domains 1/2

FOXA2:

Forkhead box protein A2

GSK3β:

Glycogen synthase kinase-3 beta

HAND2 :

Heart and neural crest derivatives expressed 2

HEY2 or CHF1:

Hairy/Enhancer-of-split related with YRPW motif protein 2

HF:

Heart failure

HIF1α :

Hypoxia-inducible factor 1 alpha

HMGA1/2:

High-mobility group AT-hook 1/2

HOPX:

HOP Homeobox

HSP:

Heat shock protein

inRNA:

Long noncoding ribonucleic acid

iPSC-CFs:

Induced pluripotent stem cell–derived cardiac fibroblasts

iPSCs:

Induced pluripotent stem cells

iPSCs-ECs:

Induced pluripotent stem cell–derived endothelial cells

iPSC-SMs:

Induced pluripotent stem cell–derived cardiomyocytes

iPSC-VSMCs:

Induced pluripotent stem cell–derived vascular smooth muscle cells

IRX4:

Iroquois homeobox 4

IWP:

Inhibitor of Wnt production

KCNA5 :

Potassium voltage-gated channel subfamily A member 5

KCNJ3 :

Potassium inwardly rectifying channel subfamily J member 3

Klf4:

Krüppel-like factor 4

LGALS3BP :

Galectin 3 binding protein

LPM:

Lateral plate mesoderm

MHC:

Major histocompatibility complex

MHC:

Myosin heavy chain

MIXL1:

Mix paired-like homeobox 1

MLC or MYL :

Myosin light chain

MMLV:

Moloney murine leukemia virus

mRNA:

Messenger ribonucleic acid

MV:

Measles virus

N C:

Neural crest

NCAM:

Neural cell adhesion molecule 1

NES:

Nestin

NFIA:

Nuclear factor IA

NPP:

Natriuretic peptide

Oct3/4 :

Octamer-binding transcription factor 3/4

OSKM:

Oct4, Sox2, Klf4, and Myc reprogramming factors

Otx2:

Orthodenticle homeobox 2

PAX6:

Oculorhombin

PBMCs:

Peripheral blood mononuclear cells

PDM:

Polydimethylsiloxane

POSTN:

Periostin

PPCM:

Peripartum cardiomyopathy

RA:

Retinoic acid

RARG:

Retinoic acid receptor gamma – RARG

RBFOX2 :

RNA binding Fox-1 homolog 2

ROCK1:

Rho-kinase inhibitor

RT-PCR:

Reverse transcriptase polymerase chain reaction

S100A10:

S100 calcium binding protein A10

SCID:

Severe combined immunodeficiency

SDF-1 or CXCL12:

Stromal cell-derived factor 1

SERPINI1 :

Serpin family I member 1

SeV:

Sendai virus

SFRP2 :

Secreted frizzled related protein 2

SHF:

Second heart field

siRNA:

Small interfering ribonucleic acid

SM22α :

Smooth muscle protein 22-alpha

SMA-α:

Smooth muscle actin alpha

SM-MHC:

Smooth muscle myosin heavy chain

SMNT:

Smoothelin

SOX17:

SRY-Box transcription factor 17

Sox2:

Sex determining region Y (SRY)-box 2

SPP1:

Secreted phosphoprotein 1

SrRNA:

Self-replicating ribonucleic acid

ssTNI:

Slow skeletal muscle isoform

SYNE2:

Spectrin repeat containing nuclear envelope protein 2

T3:

Tri-iodo-l-thyronine

TBX:

T-box transcription factor

TBXT:

Brachyury

TCF21:

Transcription factor 21

THY1:

Thy-1 cell surface antigen

TOR:

Torin

TRA:

Tumor-related antigen

TUBB3:

Tubulin beta 3

USP44:

Ubiquitin-specific peptidase 44

VCAM1:

Vascular cell adhesion molecule 1

VEGF :

Vascular endothelial growth factor

VIM:

Vimentin

VSNL1:

Visinin like 1

References

  • Abilez OJ, Tzatzalos E, Yang H, Zhao MT, Jung G, Zöllner AM, Tiburcy M et al (2018) Passive stretch induces structural and functional maturation of engineered heart muscle as predicted by computational modeling. Stem Cells 36:265–277

    Article  CAS  PubMed  Google Scholar 

  • Abujarour R, Valamehr B, Robinson M, Rezner B, Vranceanu F, Flynn P (2013) Optimized surface markers for the prospective isolation of high-quality hiPSCs using flow cytometry selection. Sci Rep 3:1179

    Article  PubMed  PubMed Central  Google Scholar 

  • Abyzov A, Mariani J, Palejev D, Zhang Y, Haney MS, Tomasini L, Ferrandino AF et al (2012) Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells. Nature 492:438–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adamiak M, Cheng G, Bobis-Wozowicz S, Zhao L, Kedracka-Krok S, Samanta A, Karnas E, Xuan YT, Skupien-Rabian B, Chen X, Jankowska U, Girgis M, Sekula M, Davani A, Lasota S, Vincent RJ, Sarna M, Newell KL, Wang OL, Dudley N, Madeja Z, Dawn B, Zuba-Surma EK (2018) Induced pluripotent stem cell (iPSC)-derived extracellular vesicles are safer and more effective for cardiac repair than iPSCs. Circ Res 122:296–309

    Article  CAS  PubMed  Google Scholar 

  • Ahmed RPH, Haider KH, Buccini S, Shujia J, Ashraf M (2011) Reprogramming of skeletal myoblasts for induction of pluripotency for tumor free cardiomyogenesis in the infarcted hear. Circ Res 109:60–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahmed RE, Anzai T, Chanthra N, Uosaki H (2020) A brief review of current maturation methods for human induced pluripotent stem Cells-derived cardiomyocytes. Front Cell Dev Biol 8:178

    Article  PubMed  PubMed Central  Google Scholar 

  • Akdis D, Saguner AM, Shah K, Wei C, Medeiros-Domingo A, von Eckardstein A, Lüscher TF, Brunckhorst C, Chen HSV, Duru F (2017) Sex hormones affect the outcome in arrhythmogenic right ventricular cardiomyopathy/dysplasia: from a stem cell-derived cardiomyocyte-based model to clinical biomarkers of disease outcome. Eur Heart J 38:1498–1508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alcamí A, Symons JA, Smith GL (2000) The vaccinia virus soluble alpha/beta interferon (IFN) receptor binds to the cell surface and protects cells from the antiviral effects of IFN. J Virol 74:11230–11239

    Article  PubMed  PubMed Central  Google Scholar 

  • Andrade AC, Wolf M, Binder HM, Gomes FG, Manstein F, Ebner-Peking P, Poupardin R, Zweigerdt R, Schallmoser K, Strunk D (2021) Hypoxic conditions promote the angiogenic potential of human induced pluripotent stem cell-derived extracellular Vesicles. Int J Mol Sci 22:3890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andueza A, Kumar S, Kim J, Kang D-W, Mumme HL, Perez JI, Villa-Roel N, Jo H (2020) Endothelial reprogramming by disturbed flow revealed by single-cell RNA and Chromatin Accessibility Study. Cell Rep 33:108491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antes TJ, Middleton RC, Luther KM, Ijichi T, Peck KA, Liu WJ, Valle J, Echavez AK, Marbán E (2018) Targeting extracellular vesicles to injured tissue using membrane cloaking and surface display. J Nanobiotechnol 16:61

    Article  Google Scholar 

  • Archer CR, Sargeant R, Basak J, Pilling J, Barnes JR, Pointon A (2018) Characterization and validation of a human 3D cardiac microtissue for the assessment of changes in cardiac pathology. Sci Rep 8:10160

    Article  PubMed  PubMed Central  Google Scholar 

  • Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R (2003) Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev 17:126–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ayoubi S, Sheikh SP, Eskildsen TV (2017) Human induced pluripotent stem cell-derived vascular smooth muscle cells: differentiation and therapeutic potential. Cardiovasc Res 113:1282–1293

    Article  CAS  PubMed  Google Scholar 

  • Baghbaderani BA, Syama A, Sivapatham R, Pei Y, Mukherjee O, Fellner T, Zeng X, Rao MS (2016) Detailed characterization of human induced pluripotent stem Cells manufactured for therapeutic applications. Stem Cell Rev Rep 12:394–420

    Article  CAS  PubMed  Google Scholar 

  • Balbi C, Vassalli G (2020) Exosomes: beyond stem cells for cardiac protection and repair. Stem Cells 38:1387–1399

    Article  PubMed  Google Scholar 

  • Ban H, Nishishita N, Fusaki N, Tabata T, Saeki K, Shikamura M, Takada N, Inoue M, Hasegawa M, Kawamata S, Nishikawa S (2011) Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors. Proc Natl Acad Sci U S A 108:14234–14239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bang JS, Choi NY, Lee M, Ko K, Lee HJ, Park YS, Jeong D, Chung H-M, Ko K (2018) Optimization of episomal reprogramming for generation of human induced pluripotent stem cells from fibroblasts. Anim Cells Syst 22:132–139

    Article  CAS  Google Scholar 

  • Bao X, Lian X, Qian T, Bhute VJ, Han T, Palecek SP (2017) Directed differentiation and long-term maintenance of epicardial cells derived from human pluripotent stem cells under fully defined conditions. Nat Protoc 12:1890–1900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barile L, Lionetti V, Cervio E, Matteucci M, Gherghiceanu M, Popescu LM, Torre T, Siclari F, Moccetti T, Vassalli G (2014) Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovasc Res 103:530–541

    Article  CAS  PubMed  Google Scholar 

  • Bazzoni G, Dejana E (2004) Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 84:869–901

    Article  CAS  PubMed  Google Scholar 

  • Bedada FB, Chan SS-K, Metzger SK, Zhang L, Zhang J, Garry DJ, Kamp TJ, Kyba M, Metzger JM (2014) Acquisition of a quantitative, stoichiometrically conserved ratiometric marker of maturation status in stem cell-derived cardiac myocytes. Stem Cell Rep 3:594–605

    Article  CAS  Google Scholar 

  • Bergenfeldt H, Stehlik J, Höglund P, Andersson B, Nilsson J (2017) Donor–recipient size matching and mortality in heart transplantation: influence of body mass index and gender. J Heart Lung Transplant 36:940–947

    Article  PubMed  Google Scholar 

  • Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisén J (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergmann O, Zdunek S, Felker A, Salehpour M, Alkass K, Bernard S, Sjostrom SL, Szewczykowska M, Jackowska T, Dos Remedios C, Malm T, Andrä M, Jashari R, Nyengaard JR, Possnert G, Jovinge S, Druid H, Frisén J (2015) Dynamics of cell generation and turnover in the human heart. Cell 161:1566–1575

    Article  CAS  PubMed  Google Scholar 

  • Berstine EG, Hooper ML, Grandchamp S, Ephrussi B (1973) Alkaline phosphatase activity in mouse teratoma. Proc Natl Acad Sci U S A 70:3899–3903

    Article  CAS  PubMed  Google Scholar 

  • Biagi D, Fantozzi ET, Campos-Oliveira JC, Naghetini MV, Ribeiro AF Jr, Rodrigues S, Ogusuku I, Vanderlinde R, Christie MLA, Mello DB, de Carvalho ACC, Valadares M, Cruvinel E, Dariolli R (2021) In situ maturated early-stage human-induced pluripotent stem cell-derived cardiomyocytes improve cardiac function by enhancing segmental contraction in infarcted Rats. J Pers Med 11:374

    Article  PubMed  PubMed Central  Google Scholar 

  • Bierer BE, Meloney LG, Ahmed HR, White SA (2022) Advancing the inclusion of underrepresented women in clinical research. Cell Rep Med 3:100553

    Article  PubMed  PubMed Central  Google Scholar 

  • Blinova K, Stohlman J, Vicente J, Chan D, Johannesen L, Hortigon-Vinagre MP, Zamora V, Smith G, Crumb WJ, Pang L, Lyn-Cook B, Ross J, Brock M, Chvatal S, Millard D, Galeotti L, Stockbridge N, Strauss DG (2016) Comprehensive translational assessment of human-induced pluripotent stem cell derived cardiomyocytes for evaluating drug-induced arrhythmias. Toxicol Sci 155:234–247

    Article  PubMed  Google Scholar 

  • Bobis-Wozowicz S, Kmiotek K, Sekula M, Kedracka-Krok S, Kamycka E, Adamiak M, Jankowska U, Madetko-Talowska A, Sarna M, Bik-Multanowski M, Kolcz J, Boruczkowski D, Madeja Z, Dawn B, Zuba-Surma EK (2015) Human induced pluripotent stem cell-derived microvesicles transmit RNAs and proteins to recipient mature heart cells modulating cell fate and behavior. Stem Cells 33:2748–2761

    Article  CAS  PubMed  Google Scholar 

  • Bollini S, Smits AM, Balbi C, Lazzarini E, Ameri P (2018) Triggering endogenous cardiac repair and regeneration via extracellular vesicle-mediated communication. Front Physiol 9:1497

    Article  PubMed  PubMed Central  Google Scholar 

  • Brambrink T, Foreman R, Welstead GG, Lengner CJ, Wernig M, Suh H, Jaenisch R (2008) Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell 2:151–159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brand T (2003) Heart development: molecular insights into cardiac specification and early morphogenesis. Dev Biol 258:1–19

    Article  CAS  PubMed  Google Scholar 

  • Buccini S, Haider KH, Ahmed RPH, Jiang S, Ashraf M (2012) Cardiac progenitors derived from reprogrammed mesenchymal stem cells contribute to angiomyogenic repair of the infarcted heart. Basic Res Cardiol 107(6):301–314

    Article  PubMed  PubMed Central  Google Scholar 

  • Filippo Buono M, von Boehmer L, Strang J, Hoerstrup SP, Emmert MY, Nugraha B (2020) Human cardiac organoids for modeling genetic cardiomyopathy. Cell 9:1733

    Article  Google Scholar 

  • Burnett SD, Blanchette AD, Grimm FA, House JS, Reif DM, Wright FA, Chiu WA, Rusyn I (2019) Population-based toxicity screening in human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol 381:114711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burridge KA, Friedman MH (2010) Environment and vascular bed origin influence differences in endothelial transcriptional profiles of coronary and iliac arteries. Am J Physiol Heart Circ Physiol 299:H837–H846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burridge PW, Keller G, Gold JD, Wu JC (2012) Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. Cell Stem Cell 10:16–28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burridge PW, Matsa E, Shukla P, Lin ZC, Churko JM, Ebert AD, Lan F, Diecke S, Huber B, Mordwinkin NM, Plews JR, Abilez OJ, Cui B, Gold JD, Wu JC (2014) Chemically defined generation of human cardiomyocytes. Nat Methods 11:855–860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burtscher I, Lickert H (2009) Foxa2 regulates polarity and epithelialization in the endoderm germ layer of the mouse embryo. Development 136:1029–1038

    Article  CAS  PubMed  Google Scholar 

  • Buta C, David R, Dressel R, Emgård M, Fuchs C, Gross U, Healy L, Hescheler J, Kolar R, Martin U, Mikkers H, Müller FJ, Schneider RK, Seiler AE, Spielmann H, Weitzer G (2013) Reconsidering pluripotency tests: do we still need teratoma assays? Stem Cell Res 11:552–562

    Article  PubMed  Google Scholar 

  • Cagavi E, Akgul Caglar T, Soztekin GI, Haider KH (2018) Patient-specific induced pluripotent stem cells for cardiac disease modelling. In: Haider KH, Aziz S (eds) Stem cells: from hype to real hope. Medicine & Life Sciences, DE GRUYTER, Berlin. (Published, 2018)

    Google Scholar 

  • Cai W, Zhang J, de Lange WJ, Gregorich ZR, Karp H, Farrell ET, Mitchell SD, Tucholski T, Lin Z, Biermann M, McIlwain SJ, Ralphe JC, Kamp TJ, Ge Y (2019) An unbiased proteomics method to assess the maturation of human pluripotent stem cell-derived cardiomyocytes. Circ Res 125:936–953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camussi G, Deregibus MC, Bruno S, Grange C, Fonsato V, Tetta C (2011) Exosome/microvesicle-mediated epigenetic reprogramming of cells. Am J Cancer Res 1:98–110

    PubMed  Google Scholar 

  • Cao F, **e X, Gollan T, Zhao L, Narsinh K, Lee RJ, Wu JC (2010) Comparison of gene-transfer efficiency in human embryonic stem cells. Mol Imaging Biol 12:15–24

    Article  PubMed  Google Scholar 

  • Caspi O, Huber I, Kehat I, Habib M, Arbel G, Gepstein A, Yankelson L, Aronson D, Beyar R, Gepstein L (2007) Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol 50:1884–1893

    Article  PubMed  Google Scholar 

  • Ceholski DK, Turnbull IC, Pothula V, Lecce L, Jarrah AA, Kho C, Lee A, Hadri L, Costa KD, Hajjar RJ, Tarzami ST (2017) CXCR4 and CXCR7 play distinct roles in cardiac lineage specification and pharmacologic β-adrenergic response. Stem Cell Res 23:77–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chandy M, Rhee JW, Ozen MO, Williams DR, Pepic L, Liu C, Zhang H, Malisa J, Lau E, Demirci U, Wu JC (2020) Atlas of exosomal microRNAs secreted from human iPSC-derived cardiac cell types. Circulation 142:1794–1796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen JC, Goldhamer DJ (2003) Skeletal muscle stem cells. Reprod Biol Endocrinol 1:101

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen CX-Q, Abdian N, Maussion G, Thomas RA, Demirova I, Cai E, Tabatabaei M, Beitel LK, Karamchandani J, Fon EA, Durcan TM (2021) A multistep workflow to evaluate newly generated iPSCs and their ability to generate different cell types. Methods Protoc 4:50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen M, Chen J, Huang W, Li C, Luo H, Xue Z, **ao Y, Wu Q, Chen C (2022) Exosomes from human induced pluripotent stem cells derived mesenchymal stem cells improved myocardial injury caused by severe acute pancreatitis through activating Akt/Nrf2/HO-1 axis. Cell Cycle 21:1578–1589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheung C, Bernardo AS, Trotter MW, Pedersen RA, Sinha S (2012) Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility. Nat Biotechnol 30:165–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiu M, Austin PC, Manuel DG, Tu JV (2010) Comparison of cardiovascular risk profiles among ethnic groups using population health surveys between 1996 and 2007. CMAJ 182:E301–E310

    Article  PubMed  PubMed Central  Google Scholar 

  • Cho S, Lee C, Skylar-Scott MA, Heilshorn SC, Wu JC (2021) Reconstructing the heart using iPSCs: engineering strategies and applications. J Mol Cell Cardiol 157:56–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chong JJ, Yang X, Don CW, Minami E, Liu YW, Weyers JJ, Mahoney WM, Van Biber B, Cook SM, Palpant NJ, Gantz JA, Fugate JA, Muskheli V, Gough GM, Vogel KW, Astley CA, Hotchkiss CE, Baldessari A, Pabon L, Reinecke H, Gill EA, Nelson V, Kiem HP, Laflamme MA, Murry CE (2014) Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature 510:273–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Christidi E, Huang H, Shafaattalab S, Maillet A, Lin E, Huang K, Laksman Z, Davis MK, Tibbits GF, Brunham LR (2020) Variation in RARG increases susceptibility to doxorubicin-induced cardiotoxicity in patient specific induced pluripotent stem cell-derived cardiomyocytes. Sci Rep 10:10363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Churko JM, Garg P, Treutlein B, Venkatasubramanian M, Haodi W, Lee J, Wessells QN, Chen S-Y, Chen W-Y, Chetal K, Mantalas G, Neff N, Jabart E, Sharma A, Nolan GP, Salomonis N, Joseph CW (2018) Defining human cardiac transcription factor hierarchies using integrated single-cell heterogeneity analysis. Nat Commun 9:4906

    Article  PubMed  PubMed Central  Google Scholar 

  • Cohen ED, Tian Y, Morrisey EE (2008) Wnt signaling: an essential regulator of cardiovascular differentiation, morphogenesis and progenitor self-renewal. Development 135:789–798

    Article  CAS  PubMed  Google Scholar 

  • Colombo M, Raposo G, Théry C (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30:255–289

    Article  CAS  PubMed  Google Scholar 

  • Colvin M, Smith JM, Hadley N, Skeans MA, Carrico R, Uccellini K, Lehman R, Robinson A, Israni AK, Snyder JJ, Kasiske BL (2018) OPTN/SRTR 2016 annual data report: heart. Am J Transplant 18:291–362

    Article  PubMed  Google Scholar 

  • Conlan RS, Pisano S, Oliveira MI, Ferrari M, Mendes Pinto I (2017) Exosomes as reconfigurable therapeutic systems. Trends Mol Med 23:636–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Connelly PJ, Azizi Z, Alipour P, Delles C, Pilote L, Raparelli V (2021) The importance of gender to understand sex differences in cardiovascular disease. Can J Cardiol 37:699–710

    Article  PubMed  Google Scholar 

  • Corral-Vázquez C, Aguilar-Quesada R, Catalina P, Lucena-Aguilar G, Ligero G, Miranda B, Carrillo-Ávila JA (2017) Cell lines authentication and mycoplasma detection as minimun quality control of cell lines in biobanking. Cell Tissue Bank 18:271–280

    Article  PubMed  PubMed Central  Google Scholar 

  • Cui H, Miao S, Esworthy T, Zhou X, Lee SJ, Liu C, Yu ZX, Fisher JP, Mohiuddin M, Zhang LG (2018) 3D bioprinting for cardiovascular regeneration and pharmacology. Adv Drug Deliv Rev 132:252–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cui N, Wu F, Lu WJ, Bai R, Ke B, Liu T, Li L, Lan F, Cui M (2019) Doxorubicin-induced cardiotoxicity is maturation dependent due to the shift from topoisomerase IIα to IIβ in human stem cell derived cardiomyocytes. J Cell Mol Med 23:4627–4639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dai B, Huang W, Xu M, Millard RW, Gao MH, Hammond HK, Menick DR, Ashraf M, Wang Y (2011) Reduced collagen deposition in infarcted myocardium facilitates induced pluripotent stem cell engraftment and angiomyogenesis for improvement of left ventricular function. J Am Coll Cardiol 58:2118–2127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dallons M, Schepkens C, Dupuis A, Tagliatti V, Colet JM (2020) New insights about doxorubicin-induced toxicity to cardiomyoblast-derived H9C2 Cells and dexrazoxane cytoprotective effect: contribution of in vitro (1)H-NMR metabonomics. Front Pharmacol 11:79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • D’Amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE (2005) Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23:1534–1541

    Article  PubMed  Google Scholar 

  • Dane DM, Cao K, Zhang Y-A, Kernstine KH, Gazdhar A, Geiser T, Hsia CCW (2020) Inhalational delivery of induced pluripotent stem cell secretome improves postpneumonectomy lung structure and function. J Appl Physiol 129:1051–1061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Devalla HD, Schwach V, Ford JW, Milnes JT, El-Haou S, Jackson C, Gkatzis K, Elliott DA, de Sousa Lopes SMC, Mummery CL, Verkerk AO, Passier R (2015) Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology. EMBO Mol Med 7:394–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dionísio F, Araújo AM, Duarte-Araújo M, de Lourdes Bastos M, de Pinho PG, Carvalho F, Costa VM (2022) Cardiotoxicity of cyclophosphamide’s metabolites: an in vitro metabolomics approach in AC16 human cardiomyocytes. Arch Toxicol 96:653–671

    Article  PubMed  Google Scholar 

  • Doppler SA, Carvalho C, Lahm H, Deutsch MA, Dreßen M, Puluca N, Lange R, Krane M (2017) Cardiac fibroblasts: more than mechanical support. J Thorac Dis 9:S36–s51

    Article  PubMed  PubMed Central  Google Scholar 

  • Downing NS, Shah ND, Neiman JH, Aminawung JA, Krumholz HM, Ross JS (2016) Participation of the elderly, women, and minorities in pivotal trials supporting 2011–2013 U.S. Food and Drug Administration approvals. Trials 17:199

    Article  PubMed  PubMed Central  Google Scholar 

  • Driscoll CB, Tonne JM, El Khatib M, Cattaneo R, Ikeda Y, Devaux P (2015) Nuclear reprogramming with a non-integrating human RNA virus. Stem Cell Res Ther 6:48

    Article  PubMed  PubMed Central  Google Scholar 

  • Dunn KK, Reichardt IM, Simmons AD, ** G, Floy ME, Hoon KM, Palecek SP (2019) Coculture of endothelial Cells with human pluripotent stem cell-derived cardiac progenitors reveals a differentiation stage-specific enhancement of cardiomyocyte maturation. Biotechnol J 14:e1800725

    Article  PubMed  PubMed Central  Google Scholar 

  • Eleuteri S, Fierabracci A (2019) Insights into the Secretome of mesenchymal stem Cells and its potential applications. Int J Mol Sci 20:4597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evseenko D, Zhu Y, Schenke-Layland K, Kuo J, Latour B, Ge S, Scholes J, Dravid G, Li X, MacLellan WR, Crooks GM (2010) Map** the first stages of mesoderm commitment during differentiation of human embryonic stem cells. Proc Natl Acad Sci U S A 107:13742–13747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fakoya AOJ, Omole AE, Satyadev N, Haider HK (2022) Induced pluripotent stem cells: progress towards clinical translation from bench to bedside. In: Haider KH (ed) Handbook of stem cell therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_31-1

    Chapter  Google Scholar 

  • Fan K, Zhang S, Zhang Y, Jun L, Holcombe M, Zhang X (2017) A machine learning assisted, label-free, non-invasive approach for somatic reprogramming in induced pluripotent stem cell colony formation detection and prediction. Sci Rep 7:13496

    Article  PubMed  PubMed Central  Google Scholar 

  • Feng C, Jia YD, Zhao XY (2013) Pluripotency of induced pluripotent stem cells. Genomics Proteomics Bioinformatics 11:299–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferreira JP, Konstam MA, McMurray JJV, Butler J, Girerd N, Rossignol P, Sharma A, Voors AA, Lam CSP, Packer M, Zannad F (2021) Dosing of losartan in men versus women with heart failure with reduced ejection fraction: the HEAAL trial. Eur J Heart Fail 23:1477–1484

    Article  CAS  PubMed  Google Scholar 

  • Feschotte C (2006) The piggyBac transposon holds promise for human gene therapy. Proc Natl Acad Sci U S A 103:14981–14982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Firulli AB, Thattaliyath BD (2002) Transcription factors in cardiogenesis: The combinations that unlock the mysteries of the heart. In: International review of cytology. Academic Press

    Google Scholar 

  • Fischer A, Schumacher N, Maier M, Sendtner M, Gessler M (2004) The notch target genes Hey1 and Hey2 are required for embryonic vascular development. Genes Dev 18:901–911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fonoudi H, Ansari H, Abbasalizadeh S, Larijani MR, Kiani S, Hashemizadeh S, Zarchi AS, Bosman A, Blue GM, Pahlavan S, Perry M, Orr Y, Mayorchak Y, Vandenberg J, Talkhabi M, Winlaw DS, Harvey RP, Aghdami N, Baharvand H (2015) A universal and robust integrated platform for the scalable production of human cardiomyocytes from pluripotent stem cells. Stem Cells Transl Med 4:1482–1494

    Article  PubMed  PubMed Central  Google Scholar 

  • Forte E, Furtado MB, Rosenthal N (2018) The interstitium in cardiac repair: role of the immune–stromal cell interplay. Nat Rev Cardiol 15:601–616

    Article  CAS  PubMed  Google Scholar 

  • Frangogiannis NG (2014) The immune system and the remodeling infarcted heart: cell biological insights and therapeutic opportunities. J Cardiovasc Pharmacol 63:185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujie Y, Fusaki N, Katayama T, Hamasaki M, Soejima Y, Soga M, Ban H, Hasegawa M, Yamashita S, Kimura S, Suzuki S, Matsuzawa T, Akari H, Era T (2014) New type of Sendai virus vector provides transgene-free iPS cells derived from chimpanzee blood. PLoS One 9:e113052

    Article  PubMed  PubMed Central  Google Scholar 

  • Funakoshi S, Miki K, Takaki T, Okubo C, Hatani T, Chonabayashi K, Nishikawa M, Takei I, Oishi A, Narita M, Hoshijima M, Kimura T, Yamanaka S, Yoshida Y (2016) Enhanced engraftment, proliferation and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes. Sci Rep 6:19111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furtado MB, Nim HT, Boyd SE, Rosenthal NA (2016) View from the heart: cardiac fibroblasts in development, scarring and regeneration. Development 143:387–397

    Article  CAS  PubMed  Google Scholar 

  • Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M (2009) Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc Jpn Acad Ser B Phys Biol Sci 85:348–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao Y, Pu J (2021) Differentiation and application of human pluripotent stem cells derived cardiovascular cells for treatment of heart diseases: promises and challenges. Frontiers in Cell and Developmental Biology 9:658088

    Article  PubMed  PubMed Central  Google Scholar 

  • Gao L, Wang L, Wei Y, Krishnamurthy P, Walcott GP, Menasché P, Zhang J (2020) Exosomes secreted by hiPSC-derived cardiac cells improve recovery from myocardial infarction in swine. Sci Transl Med 12:eaay1318

    Article  CAS  PubMed  Google Scholar 

  • Garbern JC, Helman A, Sereda R, Sarikhani M, Ahmed A, Escalante GO, Ogurlu R, Kim SL, Zimmerman JF, Cho A, MacQueen L, Bezzerides VJ, Parker KK, Melton DA, Lee RT (2020) Inhibition of mTOR signaling enhances maturation of cardiomyocytes derived from human-induced pluripotent stem cells via p53-induced quiescence. Circulation 141:285–300

    Article  CAS  PubMed  Google Scholar 

  • Garcia NA, Ontoria-Oviedo I, González-King H, Diez-Juan A, Sepúlveda P (2015) Glucose starvation in cardiomyocytes enhances exosome secretion and promotes angiogenesis in endothelial cells. PLoS One 10:e0138849

    Article  PubMed  PubMed Central  Google Scholar 

  • Gassanov N, Er F, Zagidullin N, Jankowski M, Gutkowska J, Hoppe UC (2008) Retinoid acid-induced effects on atrial and pacemaker cell differentiation and expression of cardiac ion channels. Differentiation 76:971–980

    Article  CAS  PubMed  Google Scholar 

  • Gazdhar A, Ravikumar P, Pastor J, Heller M, Ye J, Zhang J, Moe OW, Geiser T, Hsia CCW (2018) Alpha-klotho enrichment in induced pluripotent stem cell secretome contributes to antioxidative protection in acute lung injury. Stem Cells 36:616–625

    Article  CAS  PubMed  Google Scholar 

  • Ge X, Ren Y, Bartulos O, Lee MY, Yue Z, Kim KY, Li W, Amos PJ, Bozkulak EC, Iyer A, Zheng W, Zhao H, Martin KA, Kotton DN, Tellides G, Park IH, Yue L, Qyang Y (2012a) Modeling supravalvular aortic stenosis syndrome with human induced pluripotent stem cells. Circulation 126:1695–1704

    Article  PubMed  PubMed Central  Google Scholar 

  • Ge X, Wang IN, Toma I, Sebastiano V, Liu J, Butte MJ, Reijo Pera RA, Yang PC (2012b) Human amniotic mesenchymal stem cell-derived induced pluripotent stem cells may generate a universal source of cardiac cells. Stem Cells Dev 21:2798–2808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gherghiceanu M, Barad L, Novak A, Reiter I, Itskovitz-Eldor J, Binah O, Popescu LM (2011) Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: comparative ultrastructure. J Cell Mol Med 15:2539–2551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giacomelli E, Meraviglia V, Campostrini G, Cochrane A, Cao X, van Helden RWJ, Krotenberg Garcia A, Mircea M, Kostidis S, Davis RP, van Meer BJ, Jost CR, Koster AJ, Mei H, Míguez DG, Mulder AA, Ledesma-Terrón M, Pompilio G, Sala L, Salvatori DCF, Slieker RC, Sommariva E, de Vries AAF, Giera M, Semrau S, Tertoolen LGJ, Orlova VV, Bellin M, Mummery CL (2020) Human-iPSC-derived cardiac stromal cells enhance maturation in 3D cardiac microtissues and reveal non-cardiomyocyte contributions to heart disease. Cell Stem Cell 26:862–79.e11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giorgetti A, Montserrat N, Aasen T, Gonzalez F, Rodríguez-Pizà I, Vassena R, Raya A, Boué S, Barrero MJ, Corbella BA, Torrabadella M, Veiga A, Belmonte JCI (2009) Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell 5:353–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goineau S, Castagné V (2018) Electrophysiological characteristics and pharmacological sensitivity of two lines of human induced pluripotent stem cell derived cardiomyocytes coming from two different suppliers. J Pharmacol Toxicol Methods 90:58–66

    Article  CAS  PubMed  Google Scholar 

  • Gore A, Li Z, Fung H-L, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E, Lee J-H, Loh Y-H, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert ML, Junying Y, Kirkness EF, Belmonte JCI, Rossi DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LSB, Zhang K (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471:63–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grimm FA, Blanchette A, House JS, Ferguson K, Hsieh NH, Dalaijamts C, Wright AA, Anson B, Wright FA, Chiu WA, Rusyn I (2018) A human population-based organotypic in vitro model for cardiotoxicity screening. ALTEX 35:441–452

    Article  PubMed  PubMed Central  Google Scholar 

  • Gryshkova V, Lushbough I, Palmer J, Burrier R, Delaunois A, Donley E, Valentin JP (2022) microRNAs signatures as potential biomarkers of structural cardiotoxicity in human-induced pluripotent stem-cell derived cardiomyocytes. Arch Toxicol 96:2033–2047

    Article  CAS  PubMed  Google Scholar 

  • Guan X, Xu W, Zhang H, Wang Q, Yu J, Zhang R, Chen Y, **a Y, Wang J, Wang D (2020) Transplantation of human induced pluripotent stem cell-derived cardiomyocytes improves myocardial function and reverses ventricular remodeling in infarcted rat hearts. Stem Cell Res Ther 11:73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo L, Coyle L, Abrams RMC, Kemper R, Chiao ET, Kolaja KL (2013) Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci 136:581–594

    Article  CAS  PubMed  Google Scholar 

  • Gurdon JB (1962) The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Development 10:622–640

    Article  CAS  Google Scholar 

  • Haider KH, Aramini B (2020) Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy. Stem Cell Res Ther 11(1):23. https://doi.org/10.1186/s13287-019-1548-7

    Article  PubMed  PubMed Central  Google Scholar 

  • Haider KH, Najimi H (2022) Exosome-based cell-free therapy in regenerative medicine for myocardial repair. In: Haider KH (ed) Handbook of stem cell therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_9-1

    Google Scholar 

  • Haider KH, Tan T, Aziz S, Chachques JC, Sim EKW (2004) Myoblast transplantation for cardiac repair: a clinical perspective. Mol Ther 9:14–23

    Article  CAS  PubMed  Google Scholar 

  • Hall C, Gehmlich K, Denning C, Pavlovic D (2021) Complex relationship between cardiac fibroblasts and cardiomyocytes in health and disease. J Am Heart Assoc 10:e019338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamad S, Derichsweiler D, Papadopoulos S, Nguemo F, Šarić T, Sachinidis A, Brockmeier K, Hescheler J, Boukens BJ, Pfannkuche K (2019) Generation of human induced pluripotent stem cell-derived cardiomyocytes in 2D monolayer and scalable 3D suspension bioreactor cultures with reduced batch-to-batch variations. Theranostics 9:7222–7238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han JW, Yoon YS (2011) Induced pluripotent stem cells: emerging techniques for nuclear reprogramming. Antioxid Redox Signal 15:1799–1820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harrell CR, Fellabaum C, Jovicic N, Djonov V, Arsenijevic N, Volarevic V (2019) Molecular mechanisms responsible for therapeutic potential of mesenchymal stem cell-derived secretome. Cell 8:467

    Article  CAS  Google Scholar 

  • Hartman RJG, Huisman SE, den Ruijter HM (2018) Sex differences in cardiovascular epigenetics-a systematic review. Biol Sex Differ 9:19

    Article  PubMed  PubMed Central  Google Scholar 

  • Helle E, Ampuja M, Dainis A, Antola L, Temmes E, Tolvanen E, Mervaala E, Kivelä R (2021) HiPS-endothelial cells acquire cardiac endothelial phenotype in co-culture with hiPS-cardiomyocytes. Front Cell Dev Biol 9:715093

    Article  PubMed  PubMed Central  Google Scholar 

  • Hoes MF, Bomer N, Ricke-Hoch M, de Jong TV, Arevalo Gomez KF, Pietzsch S, Hilfiker-Kleiner D, van der Meer P (2020) Human iPSC-derived cardiomyocytes of peripartum patients with cardiomyopathy reveal aberrant regulation of lipid metabolism. Circulation 142:2288–2291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Horikoshi Y, Yan Y, Terashvili M, Wells C, Horikoshi H, Fujita S, Bosnjak ZJ, Bai X (2019) Fatty acid-treated induced pluripotent stem cell-derived human cardiomyocytes exhibit adult cardiomyocyte-like energy metabolism phenotypes. Cells 8:1095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hotta A, Ellis J (2008) Retroviral vector silencing during iPS cell induction: an epigenetic beacon that signals distinct pluripotent states. J Cell Biochem 105:940–948

    Article  CAS  PubMed  Google Scholar 

  • Hou X, Ma S, Fan W, Li F, Miaomiao X, Yang C, Liu F, Yan Y, Wan J, Lan F, Liao B (2022) Chemically defined and small molecules-based generation of sinoatrial node-like cells. Stem Cell Res Ther 13:158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • How CK, Chien Y, Yang KY, Shih HC, Juan CC, Yang YP, Chiou GY, Huang PI, Chang YL, Chen LK, Wang CY, Hsu HS, Chiou SH, Lee CH (2013) Induced pluripotent stem cells mediate the release of interferon gamma-induced protein 10 and alleviate bleomycin-induced lung inflammation and fibrosis. Shock 39:261–270

    Article  CAS  PubMed  Google Scholar 

  • Hu GW, Li Q, Niu X, Hu B, Liu J, Zhou SM, Guo SC, Lang HL, Zhang CQ, Wang Y, Deng ZF (2015) Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem cells attenuate limb ischemia by promoting angiogenesis in mice. Stem Cell Res Ther 6:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang CY, Maia-Joca RPM, Ong CS, Wilson I, DiSilvestre D, Tomaselli GF, Reich DH (2020) Enhancement of human iPSC-derived cardiomyocyte maturation by chemical conditioning in a 3D environment. J Mol Cell Cardiol 138:1–11

    Article  CAS  PubMed  Google Scholar 

  • Huang C-Y, Liu C-L, Ting C-Y, Chiu Y-T, Cheng Y-C, Nicholson MW, Hsieh PCH (2019) Human iPSC banking: barriers and opportunities. J Biomed Sci 26:87

    Article  PubMed  PubMed Central  Google Scholar 

  • Huo J, Wei F, Cai C, Lyn-Cook B, Pang L (2018) Sex-related differences in drug-induced QT prolongation and torsades de pointes: A new model system with human iPSC-CMs. Toxicol Sci 167:360–374

    Google Scholar 

  • Ibrahim AG, Cheng K, Marbán E (2014) Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Rep 2:606–619

    Article  CAS  Google Scholar 

  • Ibrahim AY, Mehdi Q, Abbas AO, Alashkar A, Haider KH (2016) Induced pluripotent stem cells: next generation cells for tissue regeneration. J Biomed Sci Eng 9(4):226–244

    Article  CAS  Google Scholar 

  • Ichimura K, Stan RV, Kurihara H, Sakai T (2008) Glomerular endothelial cells form diaphragms during development and pathologic conditions. J Am Soc Nephrol 19:1463–1471

    Article  PubMed  PubMed Central  Google Scholar 

  • Ikeda G, Santoso MR, Tada Y, Li AM, Vaskova E, Jung JH, OBrien C, Egan E, Ye J, Yang PC (2021) Mitochondria-rich extracellular vesicles from autologous stem cell-derived cardiomyocytes restore energetics of ischemic myocardium. J Am Coll Cardiol 77:1073–1088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ikuno T, Masumoto H, Yamamizu K, Yoshioka M, Minakata K, Ikeda T, Sakata R, Yamashita JK (2017) Efficient and robust differentiation of endothelial cells from human induced pluripotent stem cells via lineage control with VEGF and cyclic AMP. PLoS One 12:e0173271

    Article  PubMed  PubMed Central  Google Scholar 

  • Inui A, Sekine H, Sano K, Dobashi I, Yoshida A, Matsuura K, Kobayashi E, Ono M, Shimizu T (2019) Generation of a large-scale vascular bed for the in vitro creation of three-dimensional cardiac tissue. Regen Ther 11:316–323

    Article  PubMed  PubMed Central  Google Scholar 

  • Ishida M, Miyagawa S, Saito A, Fukushima S, Harada A, Ito E, Ohashi F, Watabe T, Hatazawa J, Matsuura K, Sawa Y (2019) Transplantation of human-induced pluripotent stem cell-derived Cardiomyocytes is superior to somatic stem cell therapy for restoring cardiac function and oxygen consumption in a porcine model of myocardial infarction. Transplantation 103:291–298

    Article  PubMed  PubMed Central  Google Scholar 

  • Ishii Y, Langberg J, Rosborough K, Mikawa T (2009) Endothelial cell lineages of the heart. Cell Tissue Res 335:67–73

    Article  PubMed  Google Scholar 

  • Iyer D, Gambardella L, Bernard WG, Serrano F, Mascetti VL, Pedersen RA, Talasila A, Sinha S (2015) Robust derivation of epicardium and its differentiated smooth muscle cell progeny from human pluripotent stem cells. Development 142:1528–1541

    CAS  PubMed  PubMed Central  Google Scholar 

  • James V, Nizamudeen ZA, Lea D, Dottorini T, Holmes TL, Johnson BB, Arkill KP, Denning C, Smith JGW (2021) Transcriptomic analysis of Cardiomyocyte extracellular vesicles in hypertrophic cardiomyopathy reveals differential snoRNA cargo. Stem Cells Dev 30:1215–1227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Javed Z, Maqsood MH, Yahya T, Amin Z, Acquah I, Valero-Elizondo J, Andrieni J, Dubey P, Jackson RK, Daffin MA, Cainzos-Achirica M, Hyder AA, Nasir K (2022) Race, racism, and cardiovascular health: applying a social determinants of health framework to racial/ethnic disparities in cardiovascular disease. Circ Cardiovasc Qual Outcomes 15:e007917

    Article  PubMed  Google Scholar 

  • Jia F, Wilson KD, Sun N, Gupta DM, Huang M, Li Z, Panetta NJ, Chen ZY, Robbins RC, Kay MA, Longaker MT, Wu JC (2010) A nonviral minicircle vector for deriving human iPS cells. Nat Methods 7:197–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang J, Chan YS, Loh YH, Cai J, Tong GQ, Lim CA, Robson P, Zhong S, Ng HH (2008) A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol 10:353–360

    Article  PubMed  Google Scholar 

  • Jiang YF, Chen M, Zhang NN, Yang HJ, Rui Q, Zhou YF (2018) In vitro and in vivo differentiation of induced pluripotent stem cells generated from urine-derived cells into cardiomyocytes. Biol Open 7:bio029157

    PubMed  Google Scholar 

  • Kadota S, Pabon L, Reinecke H, Murry CE (2017) In vivo maturation of human induced pluripotent stem cell-derived cardiomyocytes in neonatal and adult rat hearts. Stem Cell Rep 8:278–289

    Article  CAS  Google Scholar 

  • Kamakura T, Makiyama T, Sasaki K, Yoshida Y, Wuriyanghai Y, Chen J, Hattori T, Ohno S, Kita T, Horie M, Yamanaka S, Kimura T (2013) Ultrastructural maturation of human-induced pluripotent stem cell-derived cardiomyocytes in a long-term culture. Circ J 77:1307–1314

    Article  CAS  PubMed  Google Scholar 

  • Kanai-Azuma M, Kanai Y, Gad JM, Tajima Y, Taya C, Kurohmaru M, Sanai Y, Yonekawa H, Yazaki K, Tam PP, Hayashi Y (2002) Depletion of definitive gut endoderm in Sox17-null mutant mice. Development 129:2367–2379

    Article  CAS  PubMed  Google Scholar 

  • Karbassi E, Fenix A, Marchiano S, Muraoka N, Nakamura K, Yang X, Murry CE (2020) Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine. Nat Rev Cardiol 17:341–359

    Article  PubMed  PubMed Central  Google Scholar 

  • Kashiyama N, Miyagawa S, Fukushima S, Kawamura T, Kawamura A, Yoshida S, Harada A, Watabe T, Kanai Y, Toda K, Hatazawa J, Sawa Y (2016) Development of PET imaging to visualize activated macrophages accumulated in the transplanted iPSc-derived cardiac myocytes of allogeneic origin for detecting the immune rejection of allogeneic cell transplants in mice. PLoS One 11:e0165748

    Article  PubMed  PubMed Central  Google Scholar 

  • Kashiyama N, Miyagawa S, Fukushima S, Kawamura T, Kawamura A, Yoshida S, Eiraku S, Harada A, Matsunaga K, Watabe T, Toda K, Hatazawa J, Sawa Y (2019) MHC-mismatched allotransplantation of induced pluripotent stem cell-derived cardiomyocyte sheets to improve cardiac function in a primate ischemic cardiomyopathy model. Transplantation 103:1582–1590

    Article  CAS  PubMed  Google Scholar 

  • Kassam I, Yang W, Yang J, Visscher PM, McRae AF (2019) Tissue-specific sex differences in human gene expression. Hum Mol Genet 28:2976–2986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato R, Matsumoto M, Sasaki H, Joto R, Okada M, Ikeda Y, Kanie K, Suga M, Kinehara M, Yanagihara K, Liu Y, Uchio-Yamada K, Fukuda T, Kii H, Uozumi T, Honda H, Kiyota Y, Furue MK (2016) Parametric analysis of colony morphology of non-labelled live human pluripotent stem cells for cell quality control. Sci Rep 6:34009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kattman SJ, Witty AD, Gagliardi M, Dubois NC, Niapour M, Hotta A, Ellis J, Keller G (2011) Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8:228–240

    Article  CAS  PubMed  Google Scholar 

  • Kawaguchi S, Soma Y, Nakajima K, Kanazawa H, Tohyama S, Tabei R, Hirano A, Handa N, Yamada Y, Okuda S, Hishikawa S, Teratani T, Kunita S, Kishino Y, Okada M, Tanosaki S, Someya S, Morita Y, Tani H, Kawai Y, Yamazaki M, Ito A, Shibata R, Murohara T, Tabata Y, Kobayashi E, Shimizu H, Fukuda K, Fujita J (2021) Intramyocardial transplantation of human iPS cell-derived cardiac spheroids improves cardiac function in heart failure animals. JACC Basic Transl Sci 6:239–254

    Article  PubMed  PubMed Central  Google Scholar 

  • Kawai Y, Tohyama S, Arai K, Tamura T, Soma Y, Fukuda K, Shimizu H, Nakayama K, Kobayashi E (2022) Scaffold-free tubular engineered heart tissue from human induced pluripotent stem Cells using bio-3D printing technology in vivo. Front Cardiovasc Med 8:806215

    Article  PubMed  PubMed Central  Google Scholar 

  • Kawamura M, Miyagawa S, Fukushima S, Saito A, Miki K, Ito E, Sougawa N, Kawamura T, Daimon T, Shimizu T, Okano T, Toda K, Sawa Y (2013) Enhanced survival of transplanted human induced pluripotent stem cell-derived cardiomyocytes by the combination of cell sheets with the pedicled omental flap technique in a porcine heart. Circulation 128:S87–S94

    Article  PubMed  Google Scholar 

  • Kc P, Shah M, Shaik R, Hong Y, Zhang G (2020) Preseeding of mesenchymal stem cells increases integration of an iPSC-derived CM sheet into a cardiac matrix. ACS Biomater Sci Eng 6:6808–6818

    Article  PubMed  Google Scholar 

  • Kehl D, Generali M, Mallone A, Heller M, Uldry A-C, Cheng P, Gantenbein B, Hoerstrup SP, Weber B (2019) Proteomic analysis of human mesenchymal stromal cell secretomes: a systematic comparison of the angiogenic potential. NPJ Regen Med 4:8

    Article  PubMed  PubMed Central  Google Scholar 

  • Kenneweg F, Bang C, **ao K, Boulanger CM, Loyer X, Mazlan S, Schroen B, Hermans-Beijnsberger S, Foinquinos A, Hirt MN, Eschenhagen T, Funcke S, Stojanovic S, Genschel C, Schimmel K, Just A, Pfanne A, Scherf K, Dehmel S, Raemon-Buettner SM, Fiedler J, Thum T (2019) Long noncoding RNA-enriched vesicles secreted by hypoxic cardiomyocytes drive cardiac fibrosis. Mol Ther Nucleic Acids 18:363–374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D (2002) The human genome browser at UCSC. Genome Res 12:996–1006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kervadec A, Bellamy V, El Harane N, Arakélian L, Vanneaux V, Cacciapuoti I, Nemetalla H, Périer MC, Toeg HD, Richart A, Lemitre M, Yin M, Loyer X, Larghero J, Hagège A, Ruel M, Boulanger CM, Silvestre JS, Menasché P, Renault NK (2016) Cardiovascular progenitor-derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure. J Heart Lung Transplant 35:795–807

    Article  PubMed  Google Scholar 

  • Khan M, Nickoloff E, Abramova T, Johnson J, Verma SK, Krishnamurthy P, Mackie AR, Vaughan E, Garikipati VN, Benedict C, Ramirez V, Lambers E, Ito A, Gao E, Misener S, Luongo T, Elrod J, Qin G, Houser SR, Koch WJ, Kishore R (2015) Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circ Res 117:52–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan MS, Shahid I, Siddiqi TJ, Khan SU, Warraich HJ, Greene SJ, Butler J, Michos ED (2020) Ten-year trends in enrollment of women and minorities in pivotal trials supporting recent us food and drug administration approval of novel cardiometabolic drugs. J Am Heart Assoc 9:e015594

    Article  PubMed  PubMed Central  Google Scholar 

  • Khush KK, Kubo JT, Desai M (2012) Influence of donor and recipient sex mismatch on heart transplant outcomes: analysis of the International Society for Heart and Lung Transplantation Registry. J Heart Lung Transplant 31:459–466

    Article  PubMed  PubMed Central  Google Scholar 

  • Kido K, Ito H, Yamamoto Y, Makita K, Uchida T (2018) Cytotoxicity of propofol in human induced pluripotent stem cell-derived cardiomyocytes. J Anesth 32:120–131

    Article  PubMed  Google Scholar 

  • Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim C, Wong J, Wen J, Wang S, Wang C, Spiering S, Kan NG, Forcales S, Puri PL, Leone TC, Marine JE, Calkins H, Kelly DP, Judge DP, Chen HS (2013) Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs. Nature 494:105–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kimura M, Furukawa H, Shoji M, Shinozawa T (2019) Increased mesodermal and mesendodermal populations by BMP4 treatment facilitates human iPSC line differentiation into a cardiac lineage. J Stem Cells Regen Med 15:45–51

    PubMed  PubMed Central  Google Scholar 

  • Kitamura T, Koshino Y, Shibata F, Oki T, Nakajima H, Nosaka T, Kumagai H (2003) Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics. Exp Hematol 31:1007–1014

    Article  CAS  PubMed  Google Scholar 

  • Klaus A, Müller M, Schulz H, Saga Y, Martin JF, Birchmeier W (2012) Wnt/β-catenin and bmp signals control distinct sets of transcription factors in cardiac progenitor cells. Proc Natl Acad Sci U S A 109:10921–10926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kleinsorge M, Cyganek L (2020) Subtype-directed differentiation of human iPSCs into atrial and ventricular cardiomyocytes. STAR Protoc 1:100026

    Article  PubMed  PubMed Central  Google Scholar 

  • Klingenstein S, Klingenstein M, Kleger A, Liebau S (2020) From hair to iPSCs – a guide on How to reprogram keratinocytes and why. Curr Protoc Stem Cell Biol 55:e121

    Article  PubMed  Google Scholar 

  • Kofron CM, Mende U (2017) In vitro models of the cardiac microenvironment to study myocyte and non-myocyte crosstalk: bioinspired approaches beyond the polystyrene dish. J Physiol 595:3891–3905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kogut I, McCarthy SM, Pavlova M, Astling DP, Chen X, Jakimenko A, Jones KL, Getahun A, Cambier JC, Pasmooij AMG, Jonkman MF, Roop DR, Bilousova G (2018) High-efficiency RNA-based reprogramming of human primary fibroblasts. Nat Commun 9:745

    Article  PubMed  PubMed Central  Google Scholar 

  • Kopljar I, De Bondt A, Vinken P, Teisman A, Damiano B, Goeminne N, Van den Wyngaert I, Gallacher DJ, Hua Rong L (2017) Chronic drug-induced effects on contractile motion properties and cardiac biomarkers in human induced pluripotent stem cell-derived cardiomyocytes. Br J Pharmacol 174:3766–3779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kopljar I, Hua Rong L, Van Ammel K, Otava M, Tekle F, Teisman A, Gallacher DJ (2018) Development of a human iPSC cardiomyocyte-based scoring system for cardiac Hazard identification in early drug safety de-risking. Stem Cell Rep 11:1365–1377

    Article  CAS  Google Scholar 

  • Kramann R, Schneider RK, DiRocco DP, Machado F, Fleig S, Bondzie PA, Henderson JM, Ebert BL, Humphreys BD (2015) Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell 16:51–66

    Article  CAS  PubMed  Google Scholar 

  • Kreuser U, Buchert J, Haase A, Richter W, Diederichs S (2020) Initial WNT/β-catenin activation enhanced mesoderm commitment, extracellular matrix expression, cell aggregation and cartilage tissue yield from induced pluripotent stem Cells. Front Cell Dev Biol 8:581331

    Article  PubMed  PubMed Central  Google Scholar 

  • Kreutzer J, Viehrig M, Pölönen RP, Zhao F, Ojala M, Aalto-Setälä K, Kallio P (2020) Pneumatic unidirectional cell stretching device for mechanobiological studies of cardiomyocytes. Biomech Model Mechanobiol 19:291–303

    Article  PubMed  Google Scholar 

  • Kroll K, Chabria M, Wang K, Häusermann F, Schuler F, Polonchuk L (2017) Electro-mechanical conditioning of human iPSC-derived cardiomyocytes for translational research. Prog Biophys Mol Biol 130:212–222

    Article  CAS  PubMed  Google Scholar 

  • Kuang YL, Munoz A, Nalula G, Santostefano KE, Sanghez V, Sanchez G, Terada N, Mattis AN, Iacovino M, Iribarren C, Krauss RM, Medina MW (2019) Evaluation of commonly used ectoderm markers in iPSC trilineage differentiation. Stem Cell Res 37:101434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar A, D’Souza SS, Moskvin OV, Toh H, Wang B, Zhang J, Swanson S, Guo LW, Thomson JA, Slukvin II (2017) Specification and diversification of pericytes and smooth muscle cells from mesenchymoangioblasts. Cell Rep 19:1902–1916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurtzwald-Josefson E, Zeevi-Levin N, Rubchevsky V, Bechar Erdman N, Schwartz Rohaker O, Nahum O, Hochhauser E, Ben-Avraham B, Itskovitz-Eldor J, Aravot D, Barac YD (2020) Cardiac fibroblast-induced pluripotent stem cell-derived exosomes as a potential therapeutic mean for heart failure. Int J Mol Sci 21:7215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laco F, Woo TL, Zhong Q, Szmyd R, Ting S, Khan FJ, Chai CLL, Reuveny S, Chen A, Steve O (2018) Unraveling the inconsistencies of cardiac differentiation efficiency induced by the GSK3β inhibitor CHIR99021 in human pluripotent stem Cells. Stem Cell Rep 10:1851–1866

    Article  CAS  Google Scholar 

  • Laco F, Lam AT-L, Woo T-L, Tong G, Ho V, Soong P-L, Grishina E, Lin K-H, Reuveny S, Steve Kah-Weng O (2020) Selection of human induced pluripotent stem cells lines optimization of cardiomyocytes differentiation in an integrated suspension microcarrier bioreactor. Stem Cell Res Ther 11:118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lacorre DA, Baekkevold ES, Garrido I, Brandtzaeg P, Haraldsen G, Amalric F, Girard JP (2004) Plasticity of endothelial cells: rapid dedifferentiation of freshly isolated high endothelial venule endothelial cells outside the lymphoid tissue microenvironment. Blood 103:4164–4172

    Article  CAS  PubMed  Google Scholar 

  • Laflamme MA, Chen KY, Naumova AV, Muskheli V, Fugate JA, Dupras SK, Reinecke H, Xu C, Hassanipour M, Police S, O’Sullivan C, Collins L, Chen Y, Minami E, Gill EA, Ueno S, Yuan C, Gold J, Murry CE (2007) Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts. Nat Biotechnol 25:1015–1024

    Article  CAS  PubMed  Google Scholar 

  • Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM, Pasterkamp G, de Kleijn DP, Lim SK (2010) Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res 4:214–222

    Article  CAS  PubMed  Google Scholar 

  • Laurent LC, Ulitsky I, Slavin I, Tran H, Schork A, Morey R, Lynch C, Harness JV, Lee S, Barrero MJ, Ku S, Martynova M, Semechkin R, Galat V, Gottesfeld J, Izpisua Belmonte JC, Murry C, Keirstead HS, Park HS, Schmidt U, Laslett AL, Muller FJ, Nievergelt CM, Shamir R, Loring JF (2011) Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell 8:106–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee TH, Song SH, Kim KL, Yi JY, Shin GH, Kim JY, Kim J, Han YM, Lee SH, Lee SH, Shim SH, Suh W (2010) Functional recapitulation of smooth muscle cells via induced pluripotent stem cells from human aortic smooth muscle cells. Circ Res 106:120–128

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Serpooshan V, Tong X, Venkatraman S, Lee M, Lee J, Chirikian O, Wu JC, Wu SM, Yang F (2017a) Contractile force generation by 3D hiPSC-derived cardiac tissues is enhanced by rapid establishment of cellular interconnection in matrix with muscle-mimicking stiffness. Biomaterials 131:111–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee WH, Chen WY, Shao NY, **ao D, Qin X, Baker N, Bae HR, Wei TT, Wang Y, Shukla P, Wu H, Kodo K, Ong SG, Wu JC (2017b) Comparison of non-coding RNAs in exosomes and functional efficacy of human embryonic stem cell- versus induced pluripotent stem cell-derived cardiomyocytes. Stem Cells 35:2138–2149

    Article  CAS  PubMed  Google Scholar 

  • Lendahl U, Zimmerman LB, McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60:585–595

    Article  CAS  PubMed  Google Scholar 

  • Li RA (2012) Gene- and cell-based bio-artificial pacemaker: what basic and translational lessons have we learned? Gene Ther 19:588–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li MA, Pettitt SJ, Eckert S, Ning Z, Rice S, Cadiñanos J, Yusa K, Conte N, Bradley A (2013) The piggyBac transposon displays local and distant reintegration preferences and can cause mutations at noncanonical integration sites. Mol Cell Biol 33:1317–1330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Nguyen HV, Tsang SH (2016) Skin biopsy and patient-specific stem cell lines. Methods Mol Biol 1353:77–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Wen Y, Green M, Cabral EK, Wani P, Zhang F, Wei Y, Baer TM, Chen B (2017) Cell sex affects extracellular matrix protein expression and proliferation of smooth muscle progenitor cells derived from human pluripotent stem cells. Stem Cell Res Ther 8:156

    Article  PubMed  PubMed Central  Google Scholar 

  • Li S, Pan H, Tan C, Sun Y, Song Y, Zhang X, Yang W, Wang X, Li D, Dai Y, Ma Q, Xu C, Zhu X, Kang L, Fu Y, Xu X, Shu J, Zhou N, Han F, Qin D, Huang W, Liu Z, Yan Q (2018) Mitochondrial dysfunctions contribute to hypertrophic cardiomyopathy in patient iPSC-derived cardiomyocytes with MT-RNR2 mutation. Stem Cell Rep 10:808–821

    Article  CAS  Google Scholar 

  • Lian X, Hsiao C, Wilson G, Zhu K, Hazeltine LB, Azarin SM, Raval KK, Zhang J, Kamp TJ, Palecek SP (2012) Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci 109:E1848–E1E57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lian X, Zhang J, Azarin SM, Zhu K, Hazeltine LB, Bao X, Hsiao C, Kamp TJ, Palecek SP (2013) Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions. Nat Protoc 8:162–175

    Article  CAS  PubMed  Google Scholar 

  • Lian X, Bao X, Al-Ahmad A, Liu J, Wu Y, Dong W, Dunn KK, Shusta EV, Palecek SP (2014) Efficient differentiation of human pluripotent stem cells to endothelial progenitors via small-molecule activation of WNT signaling. Stem Cell Rep 3:804–816

    Article  CAS  Google Scholar 

  • Liang P, Lan F, Lee AS, Gong T, Sanchez-Freire V, Wang Y, Diecke S, Sallam K, Knowles JW, Wang PJ, Nguyen PK, Bers DM, Robbins RC, Wu JC (2013) Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation 127:1677–1691

    Article  CAS  PubMed  Google Scholar 

  • Liang W, Han P, Kim EH, Mak J, Zhang R, Torrente AG, Goldhaber JI, Marbán E, Cho HC (2019) Canonical Wnt signaling promotes pacemaker cell specification of cardiac mesodermal cells derived from mouse and human embryonic stem cells. Stem Cells 38:352–368

    Article  PubMed  Google Scholar 

  • Liao J, Soda Y, Sugawara A, Miura Y, Hiramoto T, Tahara M, Takishima Y, Hirose L, Hijikata Y, Miyamoto S, Takeda M, Tani K (2018) Efficient gene transduction and reprogramming of hematopoietic cells including T-cells by using a non-integrating measles virus vector. Blood 132:3494–3494

    Article  Google Scholar 

  • Lim YC, Garcia-Cardena G, Allport JR, Zervoglos M, Connolly AJ, Gimbrone MA Jr, Luscinskas FW (2003) Heterogeneity of endothelial cells from different organ sites in T-cell subset recruitment. Am J Pathol 162:1591–1601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin Y, Zou J (2020) Differentiation of Cardiomyocytes from human pluripotent stem cells in fully chemically defined conditions. STAR Protocols 1:100015

    Article  PubMed  PubMed Central  Google Scholar 

  • Litviňuková M, Talavera-López C, Maatz H, Reichart D, Worth CL, Lindberg EL, Kanda M, Polanski K, Heinig M, Lee M, Nadelmann ER, Roberts K, Tuck L, Fasouli ES, DeLaughter DM, McDonough B, Wakimoto H, Gorham JM, Samari S, Mahbubani KT, Saeb-Parsy K, Patone G, Boyle JJ, Zhang H, Zhang H, Viveiros A, Oudit GY, Bayraktar OA, Seidman JG, Seidman CE, Noseda M, Hubner N, Teichmann SA (2020) Cells of the adult human heart. Nature 588:466–472

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu R, Li D, Sun F, Rampoldi A, Maxwell JT, Wu R, Fischbach P, Castellino SM, Du Y, Fu H, Mandawat A, Xu C (2020) Melphalan induces cardiotoxicity through oxidative stress in cardiomyocytes derived from human induced pluripotent stem cells. Stem Cell Res Ther 11:470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu R, Sun F, Armand LC, Wu R, Xu C (2021) Chronic ethanol exposure induces deleterious changes in cardiomyocytes derived from human induced pluripotent stem Cells. Stem Cell Rev Rep 17:2314–2331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lodrini AM, Barile L, Rocchetti M, Altomare C (2020) Human induced pluripotent stem cells derived from a cardiac somatic source: insights for an in-vitro cardiomyocyte platform. Int J Mol Sci 21:507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu K, Seidel T, Cao-Ehlker X, Dorn T, Batcha AMN, Schneider CM, Semmler M, Volk T, Moretti A, Dendorfer A, Tomasi R (2021) Progressive stretch enhances growth and maturation of 3D stem-cell-derived myocardium. Theranostics 11:6138–6153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lui C, Chin AF, Park S, Yeung E, Kwon C, Tomaselli G, Chen Y, Hibino N (2021) Mechanical stimulation enhances development of scaffold-free, 3D-printed, engineered heart tissue grafts. J Tissue Eng Regen Med 15:503–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lund RJ, Nikula T, Rahkonen N, Närvä E, Baker D, Harrison N, Andrews P, Otonkoski T, Lahesmaa R (2012) High-throughput karyoty** of human pluripotent stem cells. Stem Cell Res 9:192–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lundy SD, Zhu WZ, Regnier M, Laflamme MA (2013) Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells. Stem Cells Dev 22:1991–2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo Y, Gao D, Wang P, Lou C, Li T, Niu W, Gao Y (2021) Optimized culture methods for isolating small extracellular vesicles derived from human induced pluripotent stem cells. J Extracell Vesicles 10:e12065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lyra-Leite DM, Gutiérrez-Gutiérrez Ó, Wang M, Zhou Y, Cyganek L, Burridge PW (2022) A review of protocols for human iPSC culture, cardiac differentiation, subtype-specification, maturation, and direct reprogramming. STAR Protocols 3:101560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma R, Liang J, Huang W, Guo L, Cai W, Wang L, Paul C, Yang HT, Kim HW, Wang Y (2018) Electrical stimulation enhances cardiac differentiation of human induced pluripotent stem cells for myocardial infarction therapy. Antioxid Redox Signal 28:371–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maas RGC, Lee S, Harakalova M, Snijders CJB, Blok WR, Goodyer JH, Doevendans PAFM, Van Laake LW, van der Velden J, Asselbergs FW, Wu JC, Sluijter JPG, Wu SM, Buikema JW (2021) Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocytes. STAR Protocols 2:100334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maddah M, Shoukat-Mumtaz U, Nassirpour S, Loewke K (2014) A system for automated, noninvasive, morphology-based evaluation of induced pluripotent stem cell cultures. J Lab Autom 19:454–460

    Article  PubMed  Google Scholar 

  • Malik ZA, Kott KS, Poe AJ, Kuo T, Chen L, Ferrara KW, Knowlton AA (2013) Cardiac myocyte exosomes: stability, HSP60, and proteomics. Am J Physiol Heart Circ Physiol 304:H954–H965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mann R, Mulligan RC, Baltimore D (1983) Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 33:153–159

    Article  CAS  PubMed  Google Scholar 

  • Marcu R, Choi YJ, Xue J, Fortin CL, Wang Y, Nagao RJ, Xu J, MacDonald JW, Bammler TK, Murry CE, Muczynski K, Stevens KR, Himmelfarb J, Schwartz SM, Zheng Y (2018) Human organ-specific endothelial cell heterogeneity. iScience 4:20–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marx U, Schenk F, Behrens J, Meyr U, Wanek P, Zang W, Schmitt R, Brüstle O, Zenke M, Klocke F (2013) Automatic production of induced pluripotent stem cells. Proc CIRP 5:2–6

    Article  Google Scholar 

  • Masumoto H, Ikuno T, Takeda M, Fukushima H, Marui A, Katayama S, Shimizu T, Ikeda T, Okano T, Sakata R, Yamashita JK (2014) Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration. Sci Rep 4:6716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathur A, Loskill P, Shao K, Huebsch N, Hong S, Marcus SG, Marks N, Mandegar M, Conklin BR, Lee LP, Healy KE (2015) Human iPSC-based cardiac microphysiological system for drug screening applications. Sci Rep 5:8883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuda Y, Takahashi K, Kamioka H, Naruse K (2018) Human gingival fibroblast feeder cells promote maturation of induced pluripotent stem cells into cardiomyocytes. Biochem Biophys Res Commun 503:1798–1804

    Article  CAS  PubMed  Google Scholar 

  • Mattapally S, Zhu W, Fast VG, Gao L, Worley C, Kannappan R, Borovjagin AV, Zhang J (2018) Spheroids of cardiomyocytes derived from human-induced pluripotent stem cells improve recovery from myocardial injury in mice. Am J Physiol Heart Circ Physiol 315:H327–Hh39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mauvais-Jarvis F, Merz NB, Barnes PJ, Brinton RD, Carrero J-J, DeMeo DL, De GJ, Vries CN, Epperson RG, Klein SL, Lonardo A, Maki PM, McCullough LD, Regitz-Zagrosek V, Regensteiner JG, Rubin JB, Sandberg K, Suzuki A (2020) Sex and gender: modifiers of health, disease, and medicine. Lancet 396:565–582

    Article  PubMed  PubMed Central  Google Scholar 

  • Menasché P (2018) Stem cell-derived exosomes and the failing heart: small cause, big effect. J Thorac Cardiovasc Surg 156:1089–1092

    Article  PubMed  Google Scholar 

  • Minami T, Aird WC (2005) Endothelial cell gene regulation. Trends Cardiovasc Med 15:174–184

    Article  CAS  PubMed  Google Scholar 

  • Minami I, Yamada K, Otsuji TG, Yamamoto T, Shen Y, Otsuka S, Kadota S, Morone N, Barve M, Asai Y, Tenkova-Heuser T, Heuser JE, Uesugi M, Aiba K, Nakatsuji N (2012) A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions. Cell Rep 2:1448–1460

    Article  CAS  PubMed  Google Scholar 

  • Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113:631–642

    Article  CAS  PubMed  Google Scholar 

  • Miyoshi N, Ishii H, Nagano H, Haraguchi N, Dewi DL, Kano Y, Nishikawa S, Tanemura M, Mimori K, Tanaka F, Saito T, Nishimura J, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M (2011) Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 8:633–638

    Article  CAS  PubMed  Google Scholar 

  • Moszynski P (2007) Measles campaign’s “historic victory” for global public health. BMJ 334:177

    Article  PubMed  PubMed Central  Google Scholar 

  • Mummery CL, Zhang J, Ng ES, Elliott DA, Elefanty AG, Kamp TJ (2012) Differentiation of human embryonic stem cells and induced pluripotent stem cells to cardiomyocytes: a methods overview. Circ Res 111:344–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakanishi M, Otsu M (2012) Development of Sendai virus vectors and their potential applications in gene therapy and regenerative medicine. Curr Gene Ther 12:410–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narsinh KH, Jia F, Robbins RC, Kay MA, Longaker MT, Wu JC (2011) Generation of adult human induced pluripotent stem cells using nonviral minicircle DNA vectors. Nat Protoc 6:78–88

    Article  CAS  PubMed  Google Scholar 

  • Natunen S, Satomaa T, Pitkänen V, Salo H, Mikkola M, Natunen J, Otonkoski T, Valmu L (2011) The binding specificity of the marker antibodies Tra-1-60 and Tra-1-81 reveals a novel pluripotency-associated type 1 lactosamine epitope. Glycobiology 21:1125–1130

    Article  CAS  PubMed  Google Scholar 

  • Neef K, Drey F, Lepperhof V, Wahlers T, Hescheler J, Choi YH, Šarić T (2021) Co-transplantation of mesenchymal stromal cells and induced pluripotent stem cell-derived Cardiomyocytes improves cardiac function after myocardial damage. Front Cardiovasc Med 8:794690

    Article  CAS  PubMed  Google Scholar 

  • Nelakanti RV, Kooreman NG, Wu JC (2015) Teratoma formation: a tool for monitoring pluripotency in stem cell research. Curr Protoc Stem Cell Biol 32:4a.8.1-4a.8.17

    Article  PubMed  PubMed Central  Google Scholar 

  • Nethercott HE, Brick DJ, Schwartz PH (2011) Immunocytochemical analysis of human pluripotent stem cells. Methods Mol Biol 767:201–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen TP, **e Y, Garfinkel A, Zhilin Q, Weiss JN (2011) Arrhythmogenic consequences of myofibroblast–myocyte coupling. Cardiovasc Res 93:242–251

    Article  PubMed  PubMed Central  Google Scholar 

  • Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Schöler H, Smith A (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95:379–391

    Article  CAS  PubMed  Google Scholar 

  • Nishiga M, Guo H, Wu JC (2018) Induced pluripotent stem cells as a biopharmaceutical factory for extracellular vesicles. Eur Heart J 39:1848–1850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nolan DJ, Ginsberg M, Israely E, Palikuqi B, Poulos MG, James D, Ding BS, Schachterle W, Liu Y, Rosenwaks Z, Butler JM, **ang J, Rafii A, Shido K, Rabbany SY, Elemento O, Rafii S (2013) Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev Cell 26:204–219

    Article  CAS  PubMed  Google Scholar 

  • Nong K, Wang W, Niu X, Hu B, Ma C, Bai Y, Wu B, Wang Y, Ai K (2016) Hepatoprotective effect of exosomes from human-induced pluripotent stem cell-derived mesenchymal stromal cells against hepatic ischemia-reperfusion injury in rats. Cytotherapy 18:1548–1559

    Article  CAS  PubMed  Google Scholar 

  • Norris CM, Tannenbaum C, Pilote L, Wong G, Cantor WJ, McMurtry MS (2019) Systematic incorporation of sex-specific information into clinical practice guidelines for the management of ST -segment-elevation myocardial infarction: feasibility and outcomes. J Am Heart Assoc 8:e011597

    Article  PubMed  PubMed Central  Google Scholar 

  • Ntai A, Baronchelli S, La Spada A, Moles A, Guffanti A, De Blasio P, Biunno I (2017) A review of research-grade human induced pluripotent stem cells qualification and biobanking processes. Biopreserv Biobank 15:384–392

    Article  PubMed  Google Scholar 

  • Nunes SS, Miklas JW, Liu J, Aschar-Sobbi R, **ao Y, Zhang B, Jiang J, Massé S, Gagliardi M, Hsieh A, Thavandiran N, Laflamme MA, Nanthakumar K, Gross GJ, Backx PH, Keller G, Radisic M (2013) Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat Methods 10:781–787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322:949–953

    Article  CAS  PubMed  Google Scholar 

  • Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, Hong H, Nakagawa M, Tanabe K, Tezuka K, Shibata T, Kunisada T, Takahashi M, Takahashi J, Saji H, Yamanaka S (2011) A more efficient method to generate integration-free human iPS cells. Nat Methods 8:409–412

    Article  CAS  PubMed  Google Scholar 

  • Ong SG, Lee WH, Zhou Y, Wu JC (2018) Mining exosomal MicroRNAs from human-induced pluripotent stem cells-derived cardiomyocytes for cardiac regeneration. Methods Mol Biol 1733:127–136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ongstad E, Kohl P (2016) Fibroblast-myocyte coupling in the heart: potential relevance for therapeutic interventions. J Mol Cell Cardiol 91:238–246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pagel W (1970) Galen and the usefulness of the parts of the body, translated from the Greek with an introduction and commentary by Margaret Tallmadge May, Ithaca, New York, Cornell University Press1968, 2 vols., pp. xv, 802, $25 (238s.). Med Hist 14:406–408

    Article  PubMed Central  Google Scholar 

  • Paige SL, Plonowska K, Xu A, Wu SM (2015) Molecular regulation of cardiomyocyte differentiation. Circ Res 116:341–353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paloschi V, Sabater-Lleal M, Middelkamp H, Vivas A, Johansson S, van der Meer A, Tenje M, Maegdefessel L (2021) Organ-on-a-chip technology: a novel approach to investigate cardiovascular diseases. Cardiovasc Res 117:2742–2754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palpant NJ, Pabon L, Friedman CE, Roberts M, Hadland B, Zaunbrecher RJ, Bernstein I, Zheng Y, Murry CE (2017) Generating high-purity cardiac and endothelial derivatives from patterned mesoderm using human pluripotent stem cells. Nat Protoc 12:15–31

    Article  CAS  PubMed  Google Scholar 

  • Pandey R, Velasquez S, Durrani S, Jiang M, Neiman M, Crocker JS, Benoit JB, Rubinstein J, Paul A, Ahmed RP (2017) MicroRNA-1825 induces proliferation of adult cardiomyocytes and promotes cardiac regeneration post ischemic injury. Am J Transl Res 9:3120–3137

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pang L (2020) Toxicity testing in the era of induced pluripotent stem cells: A perspective regarding the use of patient-specific induced pluripotent stem cell–derived cardiomyocytes for cardiac safety evaluation. Curr Opin Toxicol 23-24:50–55

    Article  Google Scholar 

  • Parikh SS, Blackwell DJ, Gomez-Hurtado N, Frisk M, Wang L, Kim K, Dahl CP, Fiane A, Tønnessen T, Kryshtal DO, Louch WE, Knollmann BC (2017) Thyroid and glucocorticoid hormones promote functional T-tubule development in human-induced pluripotent stem cell-derived cardiomyocytes. Circ Res 121:1323–1330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pasha Z, Haider KH, Ashraf M (2011) Efficient non-viral reprogramming of myoblasts to stemness with a single small molecule for generating cardiac progenitor cells. PLoS One 6(8):e23667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patsch C, Challet-Meylan L, Thoma EC, Urich E, Heckel T, O’Sullivan JF, Grainger SJ, Kapp FG, Sun L, Christensen K, **a Y, Florido MH, He W, Pan W, Prummer M, Warren CR, Jakob-Roetne R, Certa U, Jagasia R, Freskgård PO, Adatto I, Kling D, Huang P, Zon LI, Chaikof EL, Gerszten RE, Graf M, Iacone R, Cowan CA (2015) Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells. Nat Cell Biol 17:994–1003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Würdinger T, Middeldorp JM (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A 107:6328–6333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peinkofer G, Maass M, Pfannkuche K, Sachinidis A, Baldus S, Hescheler J, Saric T, Halbach M (2021) Persistence of intramyocardially transplanted murine induced pluripotent stem cell-derived cardiomyocytes from different developmental stages. Stem Cell Res Ther 12:46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinheiro-de-Sousa I, Fonseca-Alaniz MH, Teixeira SK, Rodrigues MV, Krieger JE (2022) Uncovering emergent phenotypes in endothelial cells by clustering of surrogates of cardiovascular risk factors. Sci Rep 12:1372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinto AR, Ilinykh A, Ivey MJ, Kuwabara JT, D’Antoni ML, Debuque R, Chandran A, Wang L, Arora K, Rosenthal NA, Tallquist MD (2016) Revisiting cardiac cellular composition. Circ Res 118:400–409

    Article  CAS  PubMed  Google Scholar 

  • Qi X, Zhang J, Yuan H, Xu Z, Li Q, Niu X, Hu B, Wang Y, Li X (2016) Exosomes secreted by human-induced pluripotent stem cell-derived mesenchymal stem Cells repair critical-sized bone defects through enhanced angiogenesis and osteogenesis in osteoporotic rats. Int J Biol Sci 12:836–849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiu S, Li Y, Imakura Y, Mima S, Hashita T, Iwao T, Matsunaga T (2021) An efficient method for the differentiation of human iPSC-derived endoderm toward enterocytes and hepatocytes. Cell 10:812

    Article  CAS  Google Scholar 

  • Quinn TA, Camelliti P, Rog-Zielinska EA, Siedlecka U, Poggioli T, O’Toole ET, Knöpfel T, Kohl P (2016) Electrotonic coupling of excitable and nonexcitable cells in the heart revealed by optogenetics. Proc Natl Acad Sci U S A 113:14852–14857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahl PB, Lin CY, Seila AC, Flynn RA, McCuine S, Burge CB, Sharp PA, Young RA (2010) C-Myc regulates transcriptional pause release. Cell 141:432–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raznahan A, Parikshak NN, Chandran V, Blumenthal JD, Clasen LS, Alexander-Bloch AF, Zinn AR, Wangsa D, Wise J, Murphy DGM, Bolton PF, Ried T, Ross J, Giedd JN, Geschwind DH (2018) Sex-chromosome dosage effects on gene expression in humans. Proc Natl Acad Sci 115:7398–7403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rhinn M, Dollé P (2012) Retinoic acid signalling during development. Development 139:843–858

    Article  CAS  PubMed  Google Scholar 

  • Richards DJ, Tan Y, Coyle R, Li Y, Xu R, Yeung N, Parker A, Menick DR, Tian B, Mei Y (2016) Nanowires and electrical stimulation synergistically improve functions of hiPSC cardiac spheroids. Nano Lett 16:4670–4678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rivera-Feliciano J, Lee KH, Kong SW, Rajagopal S, Ma Q, Springer Z, Izumo S, Tabin CJ, Pu WT (2006) Development of heart valves requires Gata4 expression in endothelial-derived cells. Development 133:3607–3618

    Article  CAS  PubMed  Google Scholar 

  • Rog-Zielinska EA, Norris RA, Kohl P, Markwald R (2016) The living scar – cardiac fibroblasts and the injured heart. Trends Mol Med 22:99–114

    Article  PubMed  PubMed Central  Google Scholar 

  • Rojas SV, Kensah G, Rotaermel A, Baraki H, Kutschka I, Zweigerdt R, Martin U, Haverich A, Gruh I, Martens A (2017) Transplantation of purified iPSC-derived cardiomyocytes in myocardial infarction. PLoS One 12:e0173222

    Article  PubMed  PubMed Central  Google Scholar 

  • Romagnuolo R, Masoudpour H, Porta-Sánchez A, Qiang B, Barry J, Laskary A, Qi X, Massé S, Magtibay K, Kawajiri H, Jun W, Sadikov TV, Rothberg J, Panchalingam KM, Titus E, Li R-K, Zandstra PW, Wright GA, Nanthakumar K, Ghugre NR, Keller G, Laflamme MA (2019) Human embryonic stem cell-derived cardiomyocytes regenerate the infarcted pig heart but induce ventricular tachyarrhythmias. Stem Cell Rep 12:967–981

    Article  Google Scholar 

  • Ronaldson-Bouchard K, Vunjak-Novakovic G (2018) Organs-on-a-chip: a fast track for engineered human tissues in drug development. Cell Stem Cell 22:310–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roshanbinfar K, Mohammadi Z, Sheikh-Mahdi Mesgar A, Dehghan MM, Oommen OP, Hilborn J, Engel FB (2019) Carbon nanotube doped pericardial matrix derived electroconductive biohybrid hydrogel for cardiac tissue engineering. Biomater Sci 7:3906–3917

    Article  CAS  PubMed  Google Scholar 

  • Ruan J-L, Tulloch NL, Razumova MV, Saiget M, Muskheli V, Pabon L, Reinecke H, Regnier M, Murry CE (2016) Mechanical stress conditioning and electrical stimulation promote contractility and force maturation of induced pluripotent stem cell-derived human cardiac tissue. Circulation 134:1557–1567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rubach M, Adelmann R, Haustein M, Drey F, Pfannkuche K, **ao B, Koester A, Udink ten Cate FE, Choi YH, Neef K, Fatima A, Hannes T, Pillekamp F, Hescheler J, Šarić T, Brockmeier K, Khalil M (2014) Mesenchymal stem cells and their conditioned medium improve integration of purified induced pluripotent stem cell-derived cardiomyocyte clusters into myocardial tissue. Stem Cells Dev 23:643–653

    Article  CAS  PubMed  Google Scholar 

  • Rufaihah AJ, Huang NF, Kim J, Herold J, Volz KS, Park TS, Lee JC, Zambidis ET, Reijo-Pera R, Cooke JP (2013) Human induced pluripotent stem cell-derived endothelial cells exhibit functional heterogeneity. Am J Transl Res 5:21–35

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rutenberg JB, Fischer A, Jia H, Gessler M, Zhong TP, Mercola M (2006) Developmental patterning of the cardiac atrioventricular canal by notch and hairy-related transcription factors. Development 133:4381–4390

    Article  CAS  PubMed  Google Scholar 

  • Saha S, Woodard LE, Charron EM, Welch RC, Rooney CM, Wilson MH (2015) Evaluating the potential for undesired genomic effects of the piggyBac transposon system in human cells. Nucleic Acids Res 43:1770–1782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sahoo S, Klychko E, Thorne T, Misener S, Schultz KM, Millay M, Ito A, Liu T, Kamide C, Agrawal H, Perlman H, Qin G, Kishore R, Losordo DW (2011) Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity. Circ Res 109:724–728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakamoto K, Sakatoku K, Sugimoto S, Iwasaki N, Sano Y, Yamaguchi M, Kurokawa J (2019) Continued exposure of anti-cancer drugs to human iPS cell-derived cardiomyocytes can unmask their cardiotoxic effects. J Pharmacol Sci 140:345–349

    Article  CAS  PubMed  Google Scholar 

  • Sakamoto T, Matsuura TR, Wan S, Ryba DM, Kim JU, Won KJ, Lai L, Petucci C, Petrenko N, Musunuru K, Vega RB, Kelly DP (2020) A critical role for estrogen-related receptor signaling in cardiac maturation. Circ Res 126:1685–1702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salem T, Frankman Z, Churko JM (2022) Tissue engineering techniques for induced pluripotent stem cell derived three-dimensional cardiac constructs. Tissue Eng Part B Rev 28:891–911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santoso MR, Ikeda G, Tada Y, Jung JH, Vaskova E, Sierra RG, Gati C, Goldstone AB, von Bornstaedt D, Shukla P, Wu JC, Wakatsuki S, Woo YJ, Yang PC (2020) Exosomes from induced pluripotent stem cell-derived cardiomyocytes promote autophagy for myocardial repair. J Am Heart Assoc 9:e014345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schlaeger TM, Daheron L, Brickler TR, Entwisle S, Chan K, Cianci A, DeVine A, Ettenger A, Fitzgerald K, Godfrey M, Gupta D, McPherson J, Malwadkar P, Gupta M, Bell B, Doi A, Jung N, Li X, Lynes MS, Brookes E, Cherry AB, Demirbas D, Tsankov AM, Zon LI, Rubin LL, Feinberg AP, Meissner A, Cowan CA, Daley GQ (2015) A comparison of non-integrating reprogramming methods. Nat Biotechnol 33:58–63

    Article  CAS  PubMed  Google Scholar 

  • Schwach V, Cofiño-Fabres C, Ten Den SA, Passier R (2022) Improved atrial differentiation of human pluripotent stem Cells by activation of retinoic acid receptor alpha (RARα). J Pers Med 12:628

    Article  PubMed  PubMed Central  Google Scholar 

  • Sekine K, Tsuzuki S, Yasui R, Kobayashi T, Ikeda K, Hamada Y, Eriko Kanai J, Camp G, Treutlein B, Ueno Y, Okamoto S, Taniguchi H (2020) Robust detection of undifferentiated iPSC among differentiated cells. Sci Rep 10:10293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shadrin IY, Allen BW, Qian Y, Jackman CP, Carlson AL, Juhas ME, Bursac N (2017) Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues. Nat Commun 8:1825

    Article  PubMed  PubMed Central  Google Scholar 

  • Sharma A, Burridge PW, McKeithan WL, Serrano R, Shukla P, Sayed N, Churko JM, Kitani T, Wu H, Holmström A, Matsa E, Zhang Y, Kumar A, Fan AC, Del Álamo JC, Wu SM, Moslehi JJ, Mercola M, Wu JC (2017) High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells. Sci Transl Med 9:eaaf2584

    Article  PubMed  PubMed Central  Google Scholar 

  • Shen M, Quertermous T, Fischbein MP, Joseph CW (2021) Generation of vascular smooth muscle Cells from induced pluripotent stem cells. Circ Res 128:670–686

    Article  CAS  PubMed  Google Scholar 

  • Shiba Y, Gomibuchi T, Seto T, Wada Y, Ichimura H, Tanaka Y, Ogasawara T, Okada K, Shiba N, Sakamoto K, Ido D, Shiina T, Ohkura M, Nakai J, Uno N, Kazuki Y, Oshimura M, Minami I, Ikeda U (2016) Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts. Nature 538:388–391

    Article  CAS  PubMed  Google Scholar 

  • Shinohara M, Choi H, Ibuki M, Yabe SG, Okochi H, Miyajima A, Sakai Y (2019) Endodermal differentiation of human induced pluripotent stem cells using simple dialysis culture system in suspension culture. Regen Ther 12:14–19

    Article  PubMed  PubMed Central  Google Scholar 

  • Shinozawa T, Nakamura K, Shoji M, Morita M, Kimura M, Furukawa H, Ueda H, Shiramoto M, Matsuguma K, Kaji Y, Ikushima I, Yono M, Liou S-Y, Nagai H, Nakanishi A, Yamamoto K, Izumo S (2017) Recapitulation of clinical individual susceptibility to drug-induced QT prolongation in healthy subjects using iPSC-derived cardiomyocytes. Stem Cell Rep 8:226–234

    Article  CAS  Google Scholar 

  • Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, Jaenisch R (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136:964–977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stadtfeld M, Brennand K, Hochedlinger K (2008a) Reprogramming of pancreatic beta cells into induced pluripotent stem cells. Curr Biol 18:890–894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (2008b) Induced pluripotent stem cells generated without viral integration. Science 322:945–949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stephenson M, Reich DH, Boheler KR (2020) Induced pluripotent stem cell-derived vascular smooth muscle cells. Vasc Biol 2:R1–r15

    Article  CAS  PubMed  Google Scholar 

  • Stillitano F, Hansen J, Kong C-W, Karakikes I, Funck-Brentano C, Geng L, Scott S, Reynier S, Ma W, Valogne Y, Desseaux C, Salem J-E, Jeziorowska D, Zahr N, Li R, Iyengar R, Hajjar RJ, Hulot J-S (2017) Modeling susceptibility to drug-induced long QT with a panel of subject-specific induced pluripotent stem cells. elife 6:e19406

    Article  PubMed  PubMed Central  Google Scholar 

  • Strigun A, Wahrheit J, Niklas J, Heinzle E, Noor F (2012) Doxorubicin increases oxidative metabolism in HL-1 cardiomyocytes as shown by 13C metabolic flux analysis. Toxicol Sci 125:595–606

    Article  CAS  PubMed  Google Scholar 

  • Sun SJ, Lai WH, Jiang Y, Zhen Z, Wei R, Lian Q, Liao SY, Tse HF (2021) Immunomodulation by systemic administration of human-induced pluripotent stem cell-derived mesenchymal stromal cells to enhance the therapeutic efficacy of cell-based therapy for treatment of myocardial infarction. Theranostics 11:1641–1654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swaney JS, Roth DM, Olson ER, Naugle JE, Gary Meszaros J, Insel PA (2005) Inhibition of cardiac myofibroblast formation and collagen synthesis by activation and overexpression of adenylyl cyclase. Proc Natl Acad Sci 102:437–442

    Article  CAS  PubMed  Google Scholar 

  • Taapken SM, Nisler BS, Newton MA, Sampsell-Barron TL, Leonhard KA, McIntire EM, Montgomery KD (2011) Karotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells. Nat Biotechnol 29:313–314

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  CAS  PubMed  Google Scholar 

  • Takamiya M, Haider KH, Ashraf M (2011) Identification and characterization of a novel multipotent sub-population of sca-1+ cardiac progenitor cells for myocardial regeneration. PLoS One 6(9):e25265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tallquist MD, Molkentin JD (2017) Redefining the identity of cardiac fibroblasts. Nat Rev Cardiol 14:484–491

    Article  PubMed  PubMed Central  Google Scholar 

  • Talman V, Kivelä R (2018) Cardiomyocyte-endothelial cell interactions in cardiac remodeling and regeneration. Front Cardiovasc Med 5:101

    Article  PubMed  PubMed Central  Google Scholar 

  • Tamò L, Fytianos K, Caldana F, Simillion C, Feki A, Nita I, Heller M, Geiser T, Gazdhar A (2021) Interactome analysis of iPSC secretome and its effect on macrophages in vitro. Int J Mol Sci 22:958

    Article  PubMed  PubMed Central  Google Scholar 

  • Tan Y, Richards D, Xu R, Stewart-Clark S, Mani SK, Borg TK, Menick DR, Tian B, Mei Y (2015) Silicon nanowire-induced maturation of cardiomyocytes derived from human induced pluripotent stem cells. Nano Lett 15:2765–2772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan S, Tao Z, Loo S, Li** S, Chen X, Ye L (2019) Non-viral vector based gene transfection with human induced pluripotent stem cells derived cardiomyocytes. Sci Rep 9:14404

    Article  PubMed  PubMed Central  Google Scholar 

  • Tan GW, Kondo T, Imamura K, Suga M, Enami T, Nagahashi A, Tsukita K, Inoue I, Kawaguchi J, Shu T, Inoue H (2021a) Simple derivation of skeletal muscle from human pluripotent stem cells using temperature-sensitive Sendai virus vector. J Cell Mol Med 25:9586–9596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan SH, Loo SJ, Gao Y, Tao ZH, Su LP, Wang CX, Zhang SL, Mu YH, Cui YH, Abdurrachim D, Wang WH, Lalic J, Lim KC, Bu J, Tan RS, Lee TH, Zhang J, Ye L (2021b) Thymosin β4 increases cardiac cell proliferation, cell engraftment, and the reparative potency of human induced-pluripotent stem cell-derived cardiomyocytes in a porcine model of acute myocardial infarction. Theranostics 11:7879–7895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang J, Li Y, Huang X, He L, Zhang L, Wang H, Wei Y, Wenjuan P, Xueying Tian Y, Nie SH, Wang Q-D, Lui KO, Zhou B (2018) Fate map** of Sca1+ cardiac progenitor cells in the adult mouse heart. Circulation 138:2967–2969

    Article  CAS  PubMed  Google Scholar 

  • Tao Z, Loo S, Li** S, Tan S, Tee G, Gan SU, Zhang J, Chen X, Ye L (2021) Angiopoietin-1 enhanced myocyte mitosis, engraftment, and the reparability of hiPSC-CMs for treatment of myocardial infarction. Cardiovasc Res 117:1578–1591

    Article  CAS  PubMed  Google Scholar 

  • Tchieu J, Zimmer B, Fattahi F, Amin S, Zeltner N, Chen S, Studer L (2017) A modular platform for differentiation of human PSCs into all major ectodermal lineages. Cell Stem Cell 21:399–410.e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teng X, Chen L, Chen W, Yang J, Yang Z, Shen Z (2015) Mesenchymal stem cell-derived exosomes improve the microenvironment of infarcted myocardium contributing to angiogenesis and anti-inflammation. Cell Physiol Biochem 37:2415–2424

    Article  CAS  PubMed  Google Scholar 

  • Thavapalachandran S, Le TYL, Romanazzo S, Rashid FN, Ogawa M, Kilian KA, Brown P, Pouliopoulos J, Barry AM, Fahmy P, Kelly K, Kizana E, Chong JJH (2021) Pluripotent stem cell-derived mesenchymal stromal cells improve cardiac function and vascularity after myocardial infarction. Cytotherapy 23:1074–1084

    Article  CAS  PubMed  Google Scholar 

  • Tokunaga K, Saitoh N, Goldberg IG, Sakamoto C, Yasuda Y, Yoshida Y, Yamanaka S, Nakao M (2014) Computational image analysis of colony and nuclear morphology to evaluate human induced pluripotent stem cells. Sci Rep 4:6996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tombor LS, Dimmeler S (2022) Why is endothelial resilience key to maintain cardiac health? Basic Res Cardiol 117:35

    Article  PubMed  PubMed Central  Google Scholar 

  • Ueno S, Weidinger G, Osugi T, Kohn AD, Golob JL, Pabon L, Reinecke H, Moon RT, Murry CE (2007) Biphasic role for Wnt/beta-catenin signaling in cardiac specification in zebrafish and embryonic stem cells. Proc Natl Acad Sci U S A 104:9685–9690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • van Meer BJ, de Vries H, Firth KSA, van Weerd J, Tertoolen LGJ, Karperien HBJ, Jonkheijm P, Denning C, IJzerman AP, Mummery CL (2017) Small molecule absorption by PDMS in the context of drug response bioassays. Biochem Biophys Res Commun 482:323–328

    Article  PubMed  PubMed Central  Google Scholar 

  • Vialard F, Simoni G, Aboura A, De Toffol S, Molina Gomes D, Marcato L, Serero S, Clement P, Bouhanna P, Rouleau E, Grimi B, Selva J, Gaetani E, Maggi F, Joseph A, Benzacken B, Grati FR (2011) Prenatal BACs-on-beads™: a new technology for rapid detection of aneuploidies and microdeletions in prenatal diagnosis. Prenat Diagn 31:500–508

    Article  CAS  PubMed  Google Scholar 

  • Vicencio JM, Yellon DM, Sivaraman V, Das D, Boi-Doku C, Arjun S, Zheng Y, Riquelme JA, Kearney J, Sharma V, Multhoff G, Hall AR, Davidson SM (2015) Plasma exosomes protect the myocardium from ischemia-reperfusion injury. J Am Coll Cardiol 65:1525–1536

    Article  CAS  PubMed  Google Scholar 

  • Voges HK, Mills RJ, Elliott DA, Parton RG, Porrello ER, Hudson JE (2017) Development of a human cardiac organoid injury model reveals innate regenerative potential. Development 144:1118–1127

    CAS  PubMed  Google Scholar 

  • Wakui T, Matsumoto T, Matsubara K, Kawasaki T, Yamaguchi H, Akutsu H (2017) Method for evaluation of human induced pluripotent stem cell quality using image analysis based on the biological morphology of cells. J Med Imaging (Bellingham) 4:044003

    PubMed  Google Scholar 

  • Waldenström A, Gennebäck N, Hellman U, Ronquist G (2012) Cardiomyocyte microvesicles contain DNA/RNA and convey biological messages to target cells. PLoS One 7:e34653

    Article  PubMed  PubMed Central  Google Scholar 

  • Walsh P, Truong V, Nayak S, Montivero MS, Low WC, Parr AM, Dutton JR (2020) Accelerated differentiation of human pluripotent stem cells into neural lineages via an early intermediate ectoderm population. Stem Cells 38:1400–1408

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Zhang L, Li Y, Chen L, Wang X, Guo W, Zhang X, Qin G, He SH, Zimmerman A, Liu Y, Kim IM, Weintraub NL, Tang Y (2015a) Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. Int J Cardiol 192:61–69

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Zhang L, Li Y, Chen L, Wang X, Guo W, Zhang X, Qin G, He S-h, Zimmerman A, Liu Y, Kim I-m, Weintraub NL, Tang Y (2015b) Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. Int J Cardiol 192:61–69

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang G, Yang L, Grishin D, Rios X, Ye LY, Hu Y, Li K, Zhang D, Church GM, Pu WT (2017a) Efficient, footprint-free human iPSC genome editing by consolidation of Cas9/CRISPR and piggyBac technologies. Nat Protoc 12:88–103

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Chen Y, Guan C, Zhao Z, Li Q, Yang J, Mo J, Wang B, Wei W, Yang X, Song L, Li J (2017b) Using low-risk factors to generate non-integrated human induced pluripotent stem cells from urine-derived cells. Stem Cell Res Ther 8:245

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Q, Vossen A, Ikeda Y, Devaux P (2019) Measles vector as a multigene delivery platform facilitating iPSC reprogramming. Gene Ther 26:151–164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang W, He W, Ruan Y, Geng Q (2022) First pig-to-human heart transplantation. Innovation (Camb) 3:100223

    PubMed  Google Scholar 

  • Wanjare M, Kuo F, Gerecht S (2013) Derivation and maturation of synthetic and contractile vascular smooth muscle cells from human pluripotent stem cells. Cardiovasc Res 97:321–330

    Article  CAS  PubMed  Google Scholar 

  • Wanjare M, Hou L, Nakayama KH, Kim JJ, Mezak NP, Abilez OJ, Tzatzalos E, Wu JC, Huang NF (2017) Anisotropic microfibrous scaffolds enhance the organization and function of cardiomyocytes derived from induced pluripotent stem cells. Biomater Sci 5:1567–1578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7:618–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weiss ES, Allen JG, Patel ND, Russell SD, Baumgartner WA, Shah AS, Conte JV (2009) The impact of donor-recipient sex matching on survival after orthotopic heart transplantation. Circ Heart Fail 2:401–408

    Article  PubMed  Google Scholar 

  • Wermeling DP, Selwitz AS (1993) Current issues surrounding women and minorities in drug trials. Ann Pharmacother 27:904–911

    Article  CAS  PubMed  Google Scholar 

  • Wernig M, Lengner CJ, Hanna J, Lodato MA, Steine E, Foreman R, Staerk J, Markoulaki S, Jaenisch R (2008) A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nat Biotechnol 26:916–924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilkinson DG, Bhatt S, Herrmann BG (1990) Expression pattern of the mouse T gene and its role in mesoderm formation. Nature 343:657–659

    Article  CAS  PubMed  Google Scholar 

  • Willems E, Spiering S, Davidovics H, Lanier M, **a Z, Dawson M, Cashman J, Mercola M (2011) Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. Circ Res 109:360–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams IM, Wu JC (2019) Generation of endothelial cells from human pluripotent stem cells. Arterioscler Thromb Vasc Biol 39:1317–1329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Witty AD, Mihic A, Tam RY, Fisher SA, Mikryukov A, Shoichet MS, Li RK, Kattman SJ, Keller G (2014) Generation of the epicardial lineage from human pluripotent stem cells. Nat Biotechnol 32:1026–1035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hämäläinen R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458:766–770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu S, Zhu Y, Liu H, Tang L, Ruili D, Shen Y, Feng J, Zhang K, Caiyun X, Zhang S, Chen Y, Song F, Zhu Y, Weizhong G, Liang P, Carrió I, Zhang H, Tian M (2016) In vivo dynamic metabolic changes after transplantation of induced pluripotent stem cells for ischemic injury. J Nucl Med 57:2012

    Article  CAS  PubMed  Google Scholar 

  • **n M, Davis CA, Molkentin JD, Lien CL, Duncan SA, Richardson JA, Olson EN (2006) A threshold of GATA4 and GATA6 expression is required for cardiovascular development. Proc Natl Acad Sci U S A 103:11189–11194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • **ong Q, Ye L, Zhang P, Lepley M, Tian J, Li J, Zhang L, Swingen C, Vaughan JT, Kaufman DS, Zhang J (2013) Functional consequences of human induced pluripotent stem cell therapy: myocardial ATP turnover rate in the in vivo swine heart with postinfarction remodeling. Circulation 127:997–1008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu C, Wang L, Yu Y, Yin F, Zhang X, Jiang L, Qin J (2017) Bioinspired onion epithelium-like structure promotes the maturation of cardiomyocytes derived from human pluripotent stem cells. Biomater Sci 5:1810–1819

    Article  CAS  PubMed  Google Scholar 

  • Yakerson A (2019) Women in clinical trials: a review of policy development and health equity in the Canadian context. Int J Equity Health 18:56

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang X, Rodriguez M, Pabon L, Fischer KA, Reinecke H, Regnier M, Sniadecki NJ, Ruohola-Baker H, Murry CE (2014) Tri-iodo-l-thyronine promotes the maturation of human cardiomyocytes-derived from induced pluripotent stem cells. J Mol Cell Cardiol 72:296–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang L, Geng Z, Nickel T, Johnson C, Gao L, Dutton J, Hou C, Zhang J (2016) Differentiation of human induced-pluripotent stem cells into smooth-muscle cells: two novel protocols. PLoS One 11:e0147155

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang X, Rodriguez ML, Leonard A, Sun L, Fischer KA, Wang Y, Ritterhoff J, Zhao L, Kolwicz SC Jr, Pabon L, Reinecke H, Sniadecki NJ, Tian R, Ruohola-Baker H, Xu H, Murry CE (2019) Fatty acids enhance the maturation of cardiomyocytes derived from human pluripotent stem cells. Stem Cell Rep 13:657–668

    Article  CAS  Google Scholar 

  • Ye H, Wang Q (2018) Efficient generation of non-integration and feeder-free induced pluripotent stem cells from human peripheral blood cells by Sendai virus. Cell Physiol Biochem 50:1318–1331

    Article  CAS  PubMed  Google Scholar 

  • Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL (2012) Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics 13:134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye L, Zhang S, Greder L, Dutton J, Keirstead SA, Lepley M, Zhang L, Kaufman D, Zhang J (2013) Effective cardiac myocyte differentiation of human induced pluripotent stem cells requires VEGF. PLoS One 8:e53764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye L, Chang YH, **ong Q, Zhang P, Zhang L, Somasundaram P, Lepley M, Swingen C, Su L, Wendel JS, Guo J, Jang A, Rosenbush D, Greder L, Dutton JR, Zhang J, Kamp TJ, Kaufman DS, Ge Y, Zhang J (2014) Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. Cell Stem Cell 15:750–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yechikov S, Kao HKJ, Chang CW, Pretto D, Zhang XD, Sun YH, Smithers R, Sirish P, Nolta JA, Chan JW, Chiamvimonvat N, Lieu DK (2020) NODAL inhibition promotes differentiation of pacemaker-like cardiomyocytes from human induced pluripotent stem cells. Stem Cell Res 49:102043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yiangou L, Ross ADB, Goh KJ, Vallier L (2018) Human pluripotent stem cell-derived endoderm for modeling development and clinical applications. Cell Stem Cell 22:485–499

    Article  CAS  PubMed  Google Scholar 

  • Yoon CS, Kim HK, Mishchenko NP, Vasileva EA, Fedoreyev SA, Stonik VA, Han J (2018) Spinochrome D attenuates doxorubicin-induced cardiomyocyte death via improving glutathione metabolism and attenuating oxidative stress. Mar Drugs 17:2

    Article  PubMed  PubMed Central  Google Scholar 

  • Yoshida S, Miyagawa S, Fukushima S, Kawamura T, Kashiyama N, Ohashi F, Toyofuku T, Toda K, Sawa Y (2018) Maturation of human induced pluripotent stem cell-derived cardiomyocytes by soluble factors from human mesenchymal stem cells. Mol Ther 26:2681–2695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshida S, Sumomozawa K, Nagamine K, Nishizawa M (2019) Hydrogel microchambers integrated with organic electrodes for efficient electrical stimulation of human iPSC-derived cardiomyocytes. Macromol Biosci 19:e1900060

    Article  PubMed  Google Scholar 

  • Yoshida S, Miyagawa S, Toyofuku T, Fukushima S, Kawamura T, Kawamura A, Kashiyama N, Nakamura Y, Toda K, Sawa Y (2020) Syngeneic mesenchymal stem cells reduce immune rejection after induced pluripotent stem cell-derived allogeneic cardiomyocyte transplantation. Sci Rep 10:4593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshioka N, Dowdy SF (2017) Enhanced generation of iPSCs from older adult human cells by a synthetic five-factor self-replicative RNA. PLoS One 12:e0182018

    Article  PubMed  PubMed Central  Google Scholar 

  • Yoshioka N, Gros E, Li HR, Kumar S, Deacon DC, Maron C, Muotri AR, Chi NC, Fu XD, Yu BD, Dowdy SF (2013) Efficient generation of human iPSCs by a synthetic self-replicative RNA. Cell Stem Cell 13:246–254

    Article  CAS  PubMed  Google Scholar 

  • Young MA, Larson DE, Sun C-W, George DR, Ding L, Miller CA, Lin L, Pawlik KM, Chen K, Fan X, Schmidt H, Kalicki-Veizer J, Cook LL, Swift GW, Demeter RT, Wendl MC, Sands MS, Mardis ER, Wilson RK, Townes TM, Ley TJ (2012) Background mutations in parental cells account for Most of the genetic heterogeneity of induced pluripotent stem cells. Cell Stem Cell 10:570–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, Thomson JA (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324:797–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu J, Chau KF, Vodyanik MA, Jiang J, Jiang Y (2011) Efficient feeder-free episomal reprogramming with small molecules. PLoS One 6:e17557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan Y, Weijie D, Liu J, Ma W, Zhang L, Zhimin D, Cai B (2018) Stem cell-derived exosome in cardiovascular diseases: macro roles of micro particles. Front Pharmacol 9:547

    Article  PubMed  PubMed Central  Google Scholar 

  • Yucer N, Holzapfel M, Vogel T, Lenaeus L, Ornelas L, Laury A, Sareen D, Barrett R, Karlan B, Svendsen C (2017) Directed differentiation of human induced pluripotent stem cells into fallopian tube epithelium. Sci Rep 7:10741

    Article  PubMed  PubMed Central  Google Scholar 

  • Zeng H, Wang J, Clouse H, Lagrutta A, Sannajust F (2019) HiPSC-CMs from different sex and ethnic origin donors exhibit qualitatively different responses to several classes of pharmacological challenges. J Pharmacol Toxicol Methods 99:106598

    Article  CAS  PubMed  Google Scholar 

  • Zhang X-B (2013) Cellular reprogramming of human peripheral blood Cells. Genomics Proteomics Bioinformatics 11:264–274

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang B, Pu WT (2013) The mysterious origins of coronary vessels. Cell Res 23:1063–1064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Huang CT, Chen J, Pankratz MT, ** J, Li J, Yang Y, Lavaute TM, Li XJ, Ayala M, Bondarenko GI, Du ZW, ** Y, Golos TG, Zhang SC (2010) Pax6 is a human neuroectoderm cell fate determinant. Cell Stem Cell 7:90–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Wang X, Zhu H, Kranias EG, Tang Y, Peng T, Chang J, Fan GC (2012) Hsp20 functions as a novel cardiokine in promoting angiogenesis via activation of VEGFR2. PLoS One 7:e32765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Guan J, Niu X, Hu G, Guo S, Li Q, **e Z, Zhang C, Wang Y (2015) Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J Transl Med 13:49

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Tian L, Shen M, Chengyi T, Haodi W, Mingxia G, Paik DT, Joseph CW (2019a) Generation of quiescent cardiac fibroblasts from human induced pluripotent stem cells for in vitro modeling of cardiac fibrosis. Circ Res 125:552–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Tao R, Campbell KF, Carvalho JL, Ruiz EC, Kim GC, Schmuck EG, Raval AN, da Rocha AM, Herron TJ, Jalife J, Thomson JA, Kamp TJ (2019b) Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors. Nat Commun 10:2238

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Liu Y, Liu H, Tang WH (2019c) Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci 9:19

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao L, Zhang B (2017) Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes. Sci Rep 7:44735

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao X, Chen H, **ao D, Yang H, Itzhaki I, Qin X, Chour T, Aguirre A, Lehmann K, Kim Y, Shukla P, Holmström A, Zhang JZ, Zhuge Y, Ndoye BC, Zhao M, Neofytou E, Zimmermann WH, Jain M, Wu JC (2018) Comparison of non-human primate versus human induced pluripotent stem cell-derived Cardiomyocytes for treatment of myocardial infarction. Stem Cell Rep 10:422–435

    Article  Google Scholar 

  • Zhao M-T, Shao N-Y, Garg V (2020) Subtype-specific cardiomyocytes for precision medicine: where are we now? Stem Cells 38:822–833

    Article  PubMed  Google Scholar 

  • Zhou W, Freed CR (2009) Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells 27:2667–2674

    Article  CAS  PubMed  Google Scholar 

  • Zhou T, Benda C, Duzinger S, Huang Y, Li X, Li Y, Guo X, Cao G, Chen S, Hao L, Chan Y-C, Ng K-M, Ho JC, Wieser M, Jiayan W, Redl H, Tse H-F, Grillari J, Grillari-Voglauer R, Pei D, Esteban MA (2011) Generation of induced pluripotent stem cells from urine. J Am Soc Nephrol 22:1221–1228

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhu L, Wang W, Ren C, Wang Y, Zhang G, Liu J, Wang W (2022) Cellular phenotypic transformation in heart failure caused by coronary heart disease and dilated cardiomyopathy: delineating at single-cell level. Biomedicine 10:402

    CAS  Google Scholar 

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  1. Division of Cardiac Surgery, McGill University Health Centre, Montreal, Canada

    Ida Derish & Renzo Cecere

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  1. Ida Derish
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  2. Renzo Cecere
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Correspondence to Renzo Cecere .

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  1. Department of Basic Sciences, Sulaiman Alrajhi University, AlQaseem, Saudi Arabia

    Khawaja H. Haider

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  1. Basic Sciences Department, Sulaiman AlRajhi University, AlQaseem, Saudi Arabia

    Khawaja Husnain Haider Ph.D

  2. McGill University, Montreal, QC, Canada

    Simon D. Tran

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Derish, I., Cecere, R. (2023). Multifaceted Role of Induced Pluripotent Stem Cells in Preclinical Cardiac Regeneration Research. In: Haider, K.H. (eds) Handbook of Stem Cell Applications. Springer, Singapore. https://doi.org/10.1007/978-981-99-0846-2_33-1

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