Abstract
According to the figures released by the International Diabetes Federation (IDF), there were more than 4.8 million diabetes-related deaths in 2012 alone, and a total of 371 million people were diagnosed with diabetes. Incidentally, with the number of undiagnosed and diagnosed diabetic patients increasing globally, the Kingdom of Saudi Arabia is rated as one of the top few countries with a high prevalence rate estimated at 23.9%. Insufficient availability of insulin remains the hallmark of diabetes type 1 due to autoimmune loss of functionally competent β-cells, whereas diabetes type 2 may result from a combination of insufficiency of insulin and tissue resistance to the available insulin. Islet transplantation is a gold-standard treatment for diabetic patients, but poor availability of donor islets and concerns regarding long-term survival and functional ineffectiveness of the graft have hampered the progress of this treatment strategy for diabetic patients as a routine therapeutic option. Current advances in pharmacological intervention to maintain glucose homeostasis and preserve insulin-secreting β-cells can merely provide symptomatic relief. More than a decade of research has shown that stem/progenitor cells can cross lineage restriction and differentiate to adopt morphofunctionally competent β-cells. In vitro protocols have been devised based on optimization of culture conditions or genetic modification of stem cells for their efficient differentiation to mature β-cells which can secrete insulin in a glucose-responsive manner. There is a recent surge in the interest to use pluripotent stem cells following the new less stringent legislation regarding the use of embryonic stem cells (ESCs). This has also led to the advent of protocols for the reprogramming of somatic cells to achieve pluripotency reminiscence of ESCs. Induced pluripotent stem cells (iPSCs) may provide an alternative renewable source of patient-specific β-cells for transplantation to support an inefficient intrinsic repair mechanism. Additionally, given that cellular reprogramming is a multistep event and entails diverse epigenetically unstable intermediate stages, morphofunctionally competent surrogate progenitors with β-cell characteristics without iPSC generation will provide a renewable source of progenitors for tumor-free de novo regeneration of islets. This book chapter explicitly focuses on the effect of diabetes on the functionality of the intrinsic pool of stem/progenitor cells and critically appreciates the published data defining the possibility to exploit exogenous stem cells for replacement of nonfunctional pancreatic β-cells to normalize insulin production.
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Abbreviations
- Ang-I:
-
Angiopoietin 1
- Ang-II:
-
Angiopoietin 2
- ARX:
-
Aristaless-related homeobox
- BM:
-
Bone marrow
- BMSCs:
-
Bone marrow stem cells
- CSCs:
-
Cardiac stem cells
- DPP-4:
-
Dipeptidyl peptidase-4
- EGF:
-
Epidermal growth factor
- EPCs:
-
Endothelial progenitor cells
- ESCs:
-
Embryonic stem cells
- FGF-2:
-
Fibroblast growth factor-2
- G-CSF:
-
Granulocyte colony-stimulating factor
- HGF-1:
-
Hepatocyte growth factor-1
- HO-1:
-
Hemoxygenase-1
- HSCs:
-
Hematopoietic stem cells
- hTERT:
-
Human telomerase reverse transcriptase
- IGF-1:
-
Insulin-like growth factor
- IL-1:
-
Interleukin-1
- IPCs:
-
Insulin-secreting β-cells
- iPSCs:
-
Induced pluripotent stem cells
- IRS-1:
-
Insulin receptor substrate-1
- MACE:
-
Major adverse cardiac events
- miRNA:
-
MicroRNA
- MCP-1:
-
Monocyte chemoattractant protein-1
- MSCs:
-
Mesenchymal stem cells
- Ngn-3:
-
Neurogenin-3
- Pax:
-
Paired box4
- PCL/PVA:
-
Polycaprolactone and polyvinyl alcohol
- Pdx1:
-
Pancreatic duodenal homoeobox-1
- PDGF-BB:
-
Platelet derived growth factor-BB
- PGF:
-
Placental growth factor
- PHD3:
-
Prolyl hydroxylase domain 3
- PLLA/PVA:
-
Poly-L-lactic acid and polyvinyl alcohol
- PMPs:
-
Pancreas-derived multipotent precursors
- PREPS:
-
Pancreatic resident endocrine progenitors
- REST:
-
Repressor element-1 silencing transcription factor
- SDF-1α:
-
Stromal cell-derived factor-1α
- SkM:
-
Skeletal myoblasts
- Shh:
-
Sonic hedgehog
- STZ:
-
Streptozotocin
- TNF-α:
-
Tumor necrosis factor-α
- VEGF:
-
Vascular endothelial growth factor
References
Abazari MF, Soleimanifar F, Nouri Aleagha M, Torabinejad S, Nasiri N, Khamisipour G, Amini Mahabadi J et al (2018) PCL/PVA nanofibrous scaffold improve insulin-producing cells generation from human induced pluripotent stem cells. Gene 671:50–57. https://doi.org/10.1016/j.gene.2018.05.115.
Afzal MR, Haider H, Idris NM, Jiang S, Ahmed RP, Ashraf M (2010) Preconditioning promotes survival and angiomyogenic potential of mesenchymal stem cells in the infarcted heart via nf-kappab signaling. Antioxid Redox Signal 12:693–702. https://doi.org/10.1089/ars.2009.2755
Ahmed RP, Husnain Haider K, Jiang S, Rizwan AM, Ashraf M (2010) Sonic Hedgehog gene delivery to the rodent heart promotes angiogenesis via iNOS/netrin-1/PKC pathway. PLoS One 5(1):e8576. https://doi.org/10.1371/journal.pone.0008576
Ahmed RP, Ashraf M, Buccini S, Shujia J, Haider H (2011a) Cardiac tumorigenic potential of induced pluripotent stem cells in an immunocompetent host with myocardial infarction. Regen Med 6:171–178. https://doi.org/10.2217/rme.10.103
Ahmed RP, Haider HK, Buccini S, Li L, Jiang S, Ashraf M (2011b) Reprogramming of skeletal myoblasts for induction of pluripotency for tumor-free cardiomyogenesis in the infarcted heart. Circ Res 109:60–70. https://doi.org/10.1161/CIRCRESAHA.110.240010
Albiero M, Menegazzo L, Boscaro E, Agostini C, Avogaro A, Fadini GP (2011) Defective recruitment, survival and proliferation of bone marrow-derived progenitor cells at sites of delayed diabetic wound healing in mice. Diabetologia 54:945–953. https://doi.org/10.1007/s00125-010-2007-2
Albiero M, Ciciliot S, Tedesco S, Menegazzo L, Danna M, Scattolini V, Cappellari R et al (2019) Diabetes-associated myelopoiesis drives stem cell mobilopathy through an OSM-p66Shc signaling pathway. Diabetes 68(6):1303–1314. https://doi.org/10.2337/db19-0080
Alipio Z, Liao W, Roemer EJ, Waner M, Fink LM, Ward DC, Ma Y (2010) Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (ips)-derived pancreatic beta-like cells. Proc Natl Acad Sci U S A 107:13426–13431. https://doi.org/10.1073/pnas.1007884107
Algaba-Chueca F, Maymó-Masip E, Ejarque M, Ballesteros M, Llauradó G, López C, Guarque A et al (2020) Gestational diabetes impacts fetal precursor cell responses with potential consequences for offspring. Stem Cells Transl Med 9(3):351–363. https://doi.org/10.1002/sctm.19-0242
Amer MG, Embaby AS, Karam RA, Amer MG (2018) Role of adipose tissue derived stem cells differentiated into insulin producing cells in the treatment of type I diabetes mellitus. Gene 654:87–94. https://doi.org/10.1016/j.gene.2018.02.008
Ariyanti AD, Zhang J, Marcelina O, Nugrahaningrum DA, Wang G, Kasim V, Wu S (2019) Salidroside-pretreated mesenchymal stem cells enhance diabetic wound healing by promoting paracrine function and survival of mesenchymal stem cells under hyperglycemia. Stem Cells Transl Med 8(3):404–414. https://doi.org/10.1002/sctm.18-0143
Balboa D, Prasad RB, Groop L, Otonkoski T (2019) Genome editing of human pancreatic beta cell models: problems, possibilities and outlook. Diabetologia:1–8. https://doi.org/10.1007/s00125-019-4908-z
Barcala Tabarrozzi AE, Castro CN, Dewey RA, Sogayar MC, Labriola L, Perone MJ (2013) Cell-based interventions to halt autoimmunity in type 1 diabetes mellitus. Clin Exp Immunol 171:135–146. https://doi.org/10.1111/cei.12019
Ben-Yehudah A, White C, Navara CS, Castro CA, Ize-Ludlow D, Shaffer B, Sukhwani M et al (2009) Evaluating protocols for embryonic stem cell differentiation into insulin-secreting β-cells using insulin II-GFP as a specific and noninvasive reporter. Cloning Stem Cells 11(2):245–257. https://doi.org/10.1089/clo.2008.0074
Biarnes M, Montolio M, Nacher V, Raurell M, Soler J, Montanya E (2002) Beta-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia. Diabetes 51:66–72. https://doi.org/10.2337/diabetes.51.1.66
Bone RN, Icyuz M, Zhang Y, Cui W, Wang H, Peng JB, Matthews QL, Siegal GP, Wu H (2012) Gene transfer of active akt1 by an infectivity-enhanced adenovirus impacts beta-cell survival and proliferation differentially in vitro and in vivo. Islets 4(6):366–378. https://doi.org/10.4161/isl.22721
Bruin JE, Erener S, Vela J, Hu X, Johnson JD, Kurata HT, Lynn FC, Piret JM, Asadi A, Rezania A, Kieffer TJ (2014) Characterization of polyhormonal insulin-producing cells derived in vitro from human embryonic stem cells. Stem Cell Res 12:194–208. https://doi.org/10.1016/j.scr.2013.10.003
Buccini S, Haider KH, Ahmed RP, Jiang S, Ashraf M (2012) Cardiac progenitors derived from reprogrammed mesenchymal stem cells contribute to angiomyogenic repair of the infarcted heart. Basic Res Cardiol 107:301. https://doi.org/10.1007/s00395-012-0301-5
Caballero S, Sengupta N, Afzal A, Chang K-H, Calzi SL, Guberski D, Kern TS, Grant MB (2007) Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells. Diabetes 56(4):960–967. https://doi.org/10.2337/db06-1254
Calafiore R, Montanucci P, Basta G (2014) Stem cells for pancreatic beta-cell replacement in diabetes mellitus: actual perspectives. Curr Opin Organ Transplant 19:162–168. https://doi.org/10.1097/MOT.0000000000000055
Cao H, Chu Y, Zhu H, Sun J, Pu Y, Gao Z, Yang C, Peng S, Dou Z, Hua J (2011) Characterization of immortalized mesenchymal stem cells derived from foetal porcine pancreas. Cell Prolif 44:19–32. https://doi.org/10.1111/j.1365-2184.2010.00714.x
Carey BW, Markoulaki S, Hanna J, Saha K, Gao Q, Mitalipova M, Jaenisch R (2009) Reprogramming of murine and human somatic cells using a single polycistronic vector. Proc Natl Acad Sci U S A 106:157–162. https://doi.org/10.1073/pnas.0811426106
Carlotti F, Zaldumbide A, Loomans CJ, van Rossenberg E, Engelse M, de Koning EJ, Hoeben RC (2010) Isolated human islets contain a distinct population of mesenchymal stem cells. Islets 2:164–173. https://doi.org/10.4161/isl.2.3.11449
Carpenter L, Carr C, Yang CT, Stuckey DJ, Clarke K, Watt SM (2012) Efficient differentiation of human induced pluripotent stem cells generates cardiac cells that provide protection following myocardial infarction in the rat. Stem Cells Dev 21:977–986. https://doi.org/10.1089/scd.2011.0075
Castilla DM, Liu ZJ, Tian R, Li Y, Livingstone AS, Velazquez OC (2012) A novel autologous cell-based therapy to promote diabetic wound healing. Ann Surg 256:560–572. https://doi.org/10.1097/SLA.0b013e31826a9064
Chen X, Larson CS, West J, Zhang X, Kaufman DB (2010) In vivo detection of extrapancreatic insulin gene expression in diabetic mice by bioluminescence imaging. PLoS One 5(2):e9397. https://doi.org/10.1371/journal.pone.0009397
Chen S, Shimoda M, Chen J, Matsumoto S, Grayburn PA (2012) Transient overexpression of cyclin d2/cdk4/glp1 genes induces proliferation and differentiation of adult pancreatic progenitors and mediates islet regeneration. Cell Cycle 11:695–705. https://doi.org/10.4161/cc.11.4.19120
Chen F, Li T, Sun Y, Liu Q, Yang T, Chen J, Zhu H et al (2019) Generation of insulin-secreting cells from mouse gallbladder stem cells by small molecules in vitro. Stem Cell Res Ther 10(1):1–12. https://doi.org/10.1186/s13287-019-1407-6
Cheng G, Zhu L, Mahato RI (2008) Caspase-3 gene silencing for inhibiting apoptosis in insulinoma cells and human islets. Mol Pharm 5:1093–1102. https://doi.org/10.1021/mp800093f
Chhabra P, Brayman KL (2013) Stem cell therapy to cure type 1 diabetes: from hype to hope. Stem Cells Transl Med 2:328–336. https://doi.org/10.5966/sctm.2012-0116
Choi JB, Uchino H, Azuma K, Iwashita N, Tanaka Y, Mochizuki H, Migita M, Shimada T, Kawamori R, Watada H (2003) Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells. Diabetologia 46:1366–1374. https://doi.org/10.1007/s00125-003-1182-9
Cim A, Sawyer GJ, Zhang X, Su H, Collins L, Jones P, Antoniou M, Reynes JP, Lipps HJ, Fabre JW (2012) In vivo studies on non-viral transdifferentiation of liver cells towards pancreatic beta cells. J Endocrinol 214:277–288
Cramer C, Freisinger E, Jones RK, Slakey DP, Dupin CL, Newsome ER, Alt EU, Izadpanah R (2012) Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells. Stem Cells Dev 19:1875–1884. https://doi.org/10.1089/scd.2010.0009
Dai C, Yang J, Bastacky S, **a J, Li Y, Liu Y (2004) Intravenous administration of hepatocyte growth factor gene ameliorates diabetic nephropathy in mice. J Am Soc Nephrol 15(10):2637–2647. https://doi.org/10.1097/01.ASN.0000139479.09658
Dor Y, Brown J, Martinez OI, Melton DA (2004) Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46. https://doi.org/10.1371/journal.pone.0181812
Durrani S, Konoplyannikov M, Ashraf M, Haider KH (2010) Skeletal myoblasts for cardiac repair. Regen Med 5:919–932. https://doi.org/10.2217/rme.10.65
Elsner M, Terbish T, Jorns A, Naujok O, Wedekind D, Hedrich HJ, Lenzen S (2012) Reversal of diabetes through gene therapy of diabetic rats by hepatic insulin expression via lentiviral transduction. Mol Ther 20:918–926. https://doi.org/10.1038/mt.2012.8
Emamaullee JA, Rajotte RV, Liston P, Korneluk RG, Lakey JR, Shapiro AM, Elliott JF (2005) **ap overexpression in human islets prevents early posttransplant apoptosis and reduces the islet mass needed to treat diabetes. Diabetes 54:2541–2548. https://doi.org/10.2337/diabetes.54.9.2541
Enderami SE, Kehtari M, Abazari MF, Ghoraeian P, Aleagha MN, Soleimanifar F, Soleimani M et al (2018) Generation of insulin-producing cells from human induced pluripotent stem cells on PLLA/PVA nanofiber scaffold. Artif Cells Nanomed Biotechnol 46(sup1):1062–1069. https://doi.org/10.1080/21691401.2018.1443466
Espejel S, Roll GR, McLaughlin KJ, Lee AY, Zhang JY, Laird DJ, Okita K, Yamanaka S, Willenbring H (2010) Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice. J Clin Invest 120:3120–3126. https://doi.org/10.1172/JCI43267
Fadini GP, Sartore S, Schiavon M, Albiero M, Baesso I, Cabrelle A, Agostini C, Avogaro A (2006) Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia-reperfusion injury in rats. Diabetologia 49:3075–3084. https://doi.org/10.1007/s00125-006-0401-6
Fadini GP, Albiero M, Vigili de Kreutzenberg S, Boscaro E, Cappellari R, Marescotti M, Poncina N, Agostini C, Avogaro A (2013) Diabetes impairs stem cell and proangiogenic cell mobilization in humans. Diabetes Care 36(4):943–949. https://doi.org/10.2337/dc12-1084
Fadini GP, Fiala M, Cappellari R, Danna M, Park S, Poncina N, Menegazzo L et al (2015) Diabetes limits stem cell mobilization following G-CSF but not plerixafor. Diabetes 64(8):2969–2977. https://doi.org/10.2337/db15-0077
Fang TC, Pang CY, Chiu SC, Ding DC, Tsai RK (2012) Renoprotective effect of human umbilical cord-derived mesenchymal stem cells in immunodeficient mice suffering from acute kidney injury. PLoS One 7:e46504. https://doi.org/10.1371/journal.pone.0046504
Ferraro F, Lymperi S, Méndez-Ferrer S, Saez B, Spencer JA, Yeap BY, Masselli E et al (2011) Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Sci Transl Med 3(104):104ra101. https://doi.org/10.1126/scitranslmed.3002191
Fiaschi-Taesch N, Stewart AF, Garcia-Ocana A (2007) Improving islet transplantation by gene delivery of hepatocyte growth factor (hgf) and its downstream target, protein kinase b (pkb)/akt. Cell Biochem Biophys 48:191–199. https://doi.org/10.1007/s12013-007-0024-7
Foad AM, Soleimanifar F, Aleagha MN, Torabinejad S, Nasiri N, Khamisipour G, Mahabadi JA et al (2018) PCL/PVA nanofibrous scaffold improve insulin-producing cells generation from human induced pluripotent stem cells. Gene 671:50–57. https://doi.org/10.1016/j.gene.2018.05.115
Francisco A-C, Els MM, Miriam E, Monica B, Gemma L, Carlos L, Albert G et al (2020) Gestational diabetes impacts fetal precursor cell responses with potential consequences for offspring. Stem Cells Transl Med 9(3):351–363. https://doi.org/10.1002/sctm.19-0242
Frost MS, Zehri AH, Limesand SW, Hay WH, Rozance PJ (2012) Differential effects of chronic pulsatile versus chronic constant maternal hyperglycemia on fetal pancreatic β-cells. J Preg 2012: Article ID 812094, 8 pages. https://doi.org/10.1155/2012/812094
Godfrey KJ, Mathew B, Bulman JC, Shah O, Clement S, Gallicano GI (2012) Stem cell-based treatments for type 1 diabetes mellitus: Bone marrow, embryonic, hepatic, pancreatic and induced pluripotent stem cells. Diabet Med 29:14–23. https://doi.org/10.1111/j.1464-5491.2011.03433.x
Grohová A, Dáňová K, Špíšek R, Palová-Jelínková L (2019) Cell based therapy for type 1 diabetes: should we take hyperglycemia into account? Front Immunol 10:79. https://doi.org/10.3389/fimmu.2019.00079
Guo X-J, Li F-J, He Y-Z, Hou S-F, Zhu H-B, Cheng Y, Nan Z et al (2019) Efficacy of Autologous bone marrow mononuclear cell transplantation therapy for type 2 diabetes mellitus: an updated meta-analysis. Diabetes Ther 10(2):535–547. https://doi.org/10.1007/s13300-019-0578-6
Haider HKh, Aslam M (2018) Cell-free therapy with stem cell secretions: protection, repair and regeneration of the injured myocardium. In: Husnain Haider Kh, Aziz S (eds) Stem cells: from hype to real hope. Medicine & Life Sciences, Berlin, (Published, 2018), pp 34–70
Haider HK, Jiang S, Ye L, Aziz S, Law PK, Sim EKW (2003) Human myoblasts have conditionally immunopriviledged status when transplanted for cardiac repair in a porcine heart model. Circulation 108:245
Haider HK, Jiang S, Ye L, Aziz S, Law PK, Sim EKW (2004a) Effectiveness of transient immunosuppression using cyclosporine for xenomyoblast transplantation for cardiac repair. Transplant Proc 36(1):232–235. https://doi.org/10.1016/j.transproceed.2003.11.001
Haider HK, Ye L, Jiang S, Ge R, Law PK, Chua T, Wong P, Sim EKW (2004b) Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor. J Mol Med 82(8):539–549. https://doi.org/10.1007/s00109-004-0546-z
Haider HK, Jiang S, Idris NM, Ashraf M (2008) IGF-1–overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1α/CXCR4 signaling to promote myocardial repair. Circ Res 103(11):1300–1308. https://doi.org/10.1161/CIRCRESAHA.108.186742
Haider HKh, Khan M, Sen C (2015) MicroRNAs with mega functions in cardiac remodeling and repair. In: Sen C (ed) The micro management of the matters of the heart. Elsevier Publishing, pp 569–600. https://doi.org/10.1016/b978-0-12-405544-5.00022-8, ISBN: 978-0-12-40554-5
Herreros MD, Garcia-Arranz M, Guadalajara H, De-La-Quintana P, Garcia-Olmo D (2012) Autologous expanded adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistulas: a phase iii randomized clinical trial (fatt 1: Fistula advanced therapy trial 1) and long-term evaluation. Dis Colon Rectum 55:762–772. https://doi.org/10.1097/DCR.0b013e318255364a
Hiratsuka M, Uno N, Ueda K, Kurosaki H, Imaoka N, Kazuki K, Ueno E, Akakura Y, Katoh M, Osaki M, Kazuki Y, Nakagawa M, Yamanaka S, Oshimura M (2011) Integration-free ips cells engineered using human artificial chromosome vectors. PLoS One 6:e25961. https://doi.org/10.1371/journal.pone.0025961
Ho JH, Tseng TC, Ma WH, Ong WK, Chen YF, Chen MH, Lin MW, Hong CY, Lee OK (2012) Multiple intravenous transplantations of mesenchymal stem cells effectively restore long-term blood glucose homeostasis by hepatic engraftment and beta-cell differentiation in streptozocin-induced diabetic mice. Cell Transplant 21:997–1009. https://doi.org/10.3727/096368911X603611
Hua XF, Wang YW, Tang YX, Yu SQ, ** SH, Meng XM, Li HF, Liu FJ, Sun Q, Wang HY, Li JY (2014) Pancreatic insulin-producing cells differentiated from human embryonic stem cells correct hyperglycemia in scid/nod mice, an animal model of diabetes. PLoS One 9:e102198. https://doi.org/10.1371/journal.pone.0102198
Hwang Y, Cha S-H, Hong Y, Jung AR, Jun H-S (2019) Direct differentiation of insulin-producing cells from human urine-derived stem cells. Int J Med Sci 16(12):1668. https://doi.org/10.7150/ijms.36011
Hyder A (2019) Transcriptome analysis of mesenchymal stem cells differentiated into insulin-producing cells reveals dissimilarities with pancreatic beta cells in response to glucose. J Stem Cell Rep 1(102):1–10
Ibrahim A, Mehdi MQ, Abbas AO, Alashkar A, Haider HK (2016) Induced pluripotent stem cells: next generation cells for tissue regeneration. J Biomed Sci Eng 9(4):226. https://doi.org/10.4236/jbise.2016.94017
International Diabetes Federation diabetes Atlas: https://diabetesatlas.org/en/
Ionescu LI, Alphonse RS, Arizmendi N, Morgan B, Abel M, Eaton F, Duszyk M, Vliagoftis H, Aprahamian TR, Walsh K, Thebaud B (2012) Airway delivery of soluble factors from plastic-adherent bone marrow cells prevents murine asthma. Am J Respir Cell Mol Biol 46:207–216. https://doi.org/10.1165/rcmb.2010-0391OC
Iskovich S, Goldenberg-Cohen N, Sadikov T, Yaniv I, Stein J, Askenasy N (2015) Two distinct mechanisms mediate the involvement of bone marrow cells in islet remodeling: neogenesis of insulin-producing cells and support of islet recovery. Cell Transplant 24(5):879–890. https://doi.org/10.3727/096368913X676899
Ito T, Itakura S, Todorov I, Rawson J, Asari S, Shintaku J, Nair I, Ferreri K, Kandeel F, Mullen Y (2010) Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function. Transplantation 89:1438–1445. https://doi.org/10.1097/TP.0b013e3181db09c4
James AW, Levi B, Commons GW, Glotzbach J, Longaker MT (2010) Paracrine interaction between adipose-derived stromal cells and cranial suture-derived mesenchymal cells. Plast Reconstr Surg 126:806–821. https://doi.org/10.1097/PRS.0b013e3181e5f81a
Jarajapu YPR, Caballero S, Verma A, Nakagawa T, Li Q, Grant MB (2011) Blockade of NADPH oxidase restores vasoreparative function in diabetic CD34+ cells. Invest Ophthalmol Vis Sci 52(8):5093–5104. https://doi.org/10.1167/iovs.10-70911
Jebaraj JC, Bhuvaneswari B (2020) Human pancreatic adult stem cells – is it a gleam of hope to patients with type-I diabetes mellitus? Biomed Pharmacol J 13(1):139–144. https://doi.org/10.13005/bpj/1870
Jeong Y-M, Cheng X-W, Lee S, Lee K-H, Cho H, Kang J-H, Kim W (2017) Preconditioning with far-infrared irradiation enhances proliferation, cell survival, and migration of rat bone marrow-derived stem cells via CXCR4-ERK pathways. Sci Rep 7(1):1–9. https://doi.org/10.1038/s41598-017-14219-w
** P, Zhang X, Wu Y, Li L, Yin Q, Zheng L, Zhang H, Sun C (2010) Streptozotocin-induced diabetic rat-derived bone marrow mesenchymal stem cells have impaired abilities in proliferation, paracrine, antiapoptosis, and myogenic differentiation. Transplant Proc 42:2745–2752. https://doi.org/10.1016/j.transproceed.2010.05.145
José VS, Monnerat G, Guerra B, Paredes BD, Brunswick THK, de Carvalho ACC, Medei E (2017) Bone-marrow-derived mesenchymal stromal cells (MSC) from diabetic and nondiabetic rats have similar therapeutic potentials. Arq Bras Cardiol 109(6):579–589. https://doi.org/10.5935/abc.20170176
Jung Y, Zhou R, Kato T, Usui JK, Muratani M, Oishi H, Margarete MS, Heck, Takahashi S (2018) Isl1 β overexpression with key β cell transcription factors enhances glucose-responsive hepatic insulin production and secretion. Endocrinology 159(2):869–882. https://doi.org/10.1210/en.2017-00663
Kadam S, Govindasamy V, Bhonde R (2012) Generation of functional islets from human umbilical cord and placenta derived mesenchymal stem cells. Methods Mol Biol 879:291–313. https://doi.org/10.1007/978-1-61779-815-317
Kaitsuka T, Noguchi H, Shiraki N, Kubo T, Wei FY, Hakim F, Kume S, Tomizawa K (2014) Generation of functional insulin-producing cells from mouse embryonic stem cells through 804g cell-derived extracellular matrix and protein transduction of transcription factors. Stem Cells Transl Med 3:114–127. https://doi.org/10.5966/sctm.2013-0075
Kane NM, Thrasher AJ, Angelini GD, Emanueli C (2014) Concise review: microRNAs as modulators of stem cells and angiogenesis. Stem Cells 32(5):1059–1066. https://doi.org/10.1002/stem.1629
Karaöz E, Doğan BC, Aksoy A, Gacar G, Akyüz S, Ayhan S, Seda Z et al (2010) Isolation and in vitro characterisation of dental pulp stem cells from natal teeth. Histochem Cell Biol 133(1):95. https://doi.org/10.1007/s00418-009-0646-5
Karaoz E, Ayhan S, Gacar G, Aksoy A, Duruksu G, Okcu A, Demircan PC, Sariboyaci AE, Kaymaz F, Kasap M (2010) Isolation and characterization of stem cells from pancreatic islet: pluripotency, differentiation potential and ultrastructural characteristics. Cytotherapy 12:288–302. https://doi.org/10.3109/14653240903580296
Karnieli O, Izhar-Prato Y, Bulvik S, Efrat S (2007) Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells 25:2837–2844. https://doi.org/10.1634/stemcells.2007-0164
Karolina DS, Tavintharan S, Armugam A, Sepramaniam S, Li SPT, Wong MTK, Lim SC et al (2012) Circulating miRNA profiles in patients with metabolic syndrome. J Clin Endocrinol Metab 97(12):E2271–E2276. https://doi.org/10.1210/jc.2012-1996
Katagi M, Terashima T, Okano J, Urabe H, Nakae Y, Ogawa N, Udagawa J et al (2014) Hyperglycemia induces abnormal gene expression in hematopoietic stem cells and their progeny in diabetic neuropathy. FEBS Lett 588(6):1080–1086. https://doi.org/10.1016/j.febslet.2014.02.030
Kawamura M, Miyagawa S, Miki K, Saito A, Fukushima S, Higuchi T, Kawamura T, Kuratani T, Daimon T, Shimizu T, Okano T, Sawa Y (2012) Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation 126:S29–S37. https://doi.org/10.1161/CIRCULATIONAHA.111.084343
Keats E, Khan ZA (2012) Unique responses of stem cell-derived vascular endothelial and mesenchymal cells to high levels of glucose. PLoS One 7(6):e38752. https://doi.org/10.1371/journal.pone.0038752
Kim HW, Haider HK, Jiang S, Ashraf M (2009) Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2. J Biol Chem 284(48):33161–33168. https://doi.org/10.1074/jbc.M109.020925
Kim H, Han JW, Lee JY, Choi YJ, Sohn YD, Song M, Yoon YS (2015) Diabetic Mesenchymal Stem Cells Are Ineffective for Improving Limb Ischemia Due to Their Impaired Angiogenic Capability. Cell Transplant 24(8):1571–84. https://doi.org/10.3727/096368914X682792
Kim HW, Jiang S, Ashraf M, Haider HK (2012a) Stem cell-based delivery of Hypoxamir-210 to the infarcted heart: implications on stem cell survival and preservation of infarcted heart function. J Mol Med 90(9):997–1010. https://doi.org/10.1007/s00109-012-0920-1
Kim SJ, Choi YS, Ko ES, Lim SM, Lee CW, Kim DI (2012b) Glucose-stimulated insulin secretion of various mesenchymal stem cells after insulin-producing cell differentiation. J Biosci Bioeng 113:771–777. https://doi.org/10.1016/j.jbiosc.2012.02.007
Kim Y, Alice Y, Rim A, Yi H, Park N, Park S-H, Ju JH (2016) The generation of human induced pluripotent stem cells from blood cells: an efficient protocol using serial plating of reprogrammed cells by centrifugation. Stem Cells Int. https://doi.org/10.1155/2016/1329459
Kirk K, Hao E, Lahmy R, Itkin-Ansari P (2014) Human embryonic stem cell derived islet progenitors mature inside an encapsulation device without evidence of increased biomass or cell escape. Stem Cell Res 12:807–814. https://doi.org/10.1016/j.scr.2014.03.003
Kojima H, Fujimiya M, Matsumura K, Nakahara T, Hara M, Chan L (2004) Extrapancreatic insulin-producing cells in multiple organs in diabetes. Proc Natl Acad Sci 101(8):2458–2463. https://doi.org/10.1073/pnas.0308690100
Konoplyannikov M, Haider KH, Lai VK, Ahmed RP, Jiang S, Ashraf M (2013) Activation of diverse signaling pathways by ex-vivo delivery of multiple cytokines for myocardial repair. Stem Cells Dev 22:204–215. https://doi.org/10.1089/scd.2011.0575
Krankel N, Adams V, Linke A, Gielen S, Erbs S, Lenk K, Schuler G, Hambrecht R (2005) Hyperglycemia reduces survival and impairs function of circulating blood-derived progenitor cells. Arterioscler Thromb Vasc Biol 25:698–703. https://doi.org/10.1161/01.ATV.0000156401.04325.8f
Kredo-Russo S, Mandelbaum AD, Ness A, Alon I, Lennox KA, Behlke MA, Hornstein E (2012) Pancreas-enriched mirna refines endocrine cell differentiation. Development 139:3021–3031. https://doi.org/10.1242/dev.080127
Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, Young H, Richardson M, Smart NG, Cunningham J, Agulnick AD, D’Amour KA, Carpenter MK, Baetge EE (2008) Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 26:443–452
Kuise T, Noguchi H, Tazawa H, Kawai T, Iwamuro M, Saitoh I, Kataoka HU, Watanabe M, Noguchi Y, Fujiwara T (2014) Establishment of a pancreatic stem cell line from fibroblast-derived induced pluripotent stem cells. Biomed Eng Online 13:64. https://doi.org/10.1186/1475-925X-13-64
Kuki S, Imanishi T, Kobayashi K, Matsuo Y, Obana M, Akasaka T (2006) Hyperglycemia accelerated endothelial progenitor cell senescence via the activation of p38 mitogen-activated protein kinase. Circ J 70:1076–1081. https://doi.org/10.1253/circj.70.1076
Kunisato A, Wakatsuki M, Kodama Y, Shinba H, Ishida I, Nagao K (2010) Generation of induced pluripotent stem cells by efficient reprogramming of adult bone marrow cells. Stem Cells Dev 19:229–238. https://doi.org/10.1089/scd.2009.0149
Lahmy R, Soleimani M, Sanati MH, Behmanesh M, Kouhkan F, Mobarra N (2014) Mirna-375 promotes beta pancreatic differentiation in human induced pluripotent stem (hips) cells. Mol Biol Rep 41:2055–2066. https://doi.org/10.1007/s11033-014-3054-4
Lai VK, Ashraf M, Jiang S, Haider HK (2012) MicroRNA-143 is a critical regulator of cell cycle activity in stem cells with co-overexpression of Akt and angiopoietin-1 via transcriptional regulation of Erk5/cyclin D1 signaling. Cell Cycle 11(4):767–777. https://doi.org/10.4161/cc.11.4.19211
Lechner A, Yang Y-G, Blacken RA, Wang L, Nolan AL, Habener JF (2004) No evidence for significant transdifferentiation of bone marrow into pancreatic β-cells in vivo. Diabetes 53(3):616–623. https://doi.org/10.2337/diabetes.53.3.616
Lee BW, Lee M, Chae HY, Lee S, Kang JG, Kim CS, Lee SJ, Yoo HJ, Ihm SH (2011) Effect of hypoxia-inducible vegf gene expression on revascularization and graft function in mouse islet transplantation. Transplant Int 24:307–314. https://doi.org/10.1111/j.1432-2277.2010.01194.x
Lee S, Jeong S, Lee C, Oh J, Kim SE (2016) Mesenchymal stem cells derived from human exocrine pancreas spontaneously express pancreas progenitor-cell markers in a cell-passage-dependent manner. Stem Cells Int 2016(2016)
Legøy TA, Vethe H, Abadpour S, Strand BL, Scholz H, Paulo JA, Ræder H et al (2020) Encapsulation boosts islet-cell signature in differentiating human induced pluripotent stem cells via integrin signalling. Sci Rep 10(1):1–16. https://doi.org/10.1038/s41598-019-57305-x
Lei Y, Haider HK, Tan R-S, Su LP, Law PK, Zhang W, Sim EKW (2008) Angiomyogenesis using liposome based vascular endothelial growth factor-165 transfection with skeletal myoblast for cardiac repair. Biomaterials 29(13):2125–2137. https://doi.org/10.1016/j.biomaterials.2008.01.014
Lei Y, Lee KO, Su LP, Toh WC, Haider HK, Law PK, Zhang W, Chan SP, Sim EKW (2009) Skeletal myoblast transplantation for attenuation of hyperglycaemia, hyperinsulinaemia and glucose intolerance in a mouse model of type 2 diabetes mellitus. Diabetologia 52(9):1925–1934. https://doi.org/10.1007/s00125-009-1421-9
Leon-Quinto T, Jones J, Skoudy A, Burcin M, Soria B (2004) In vitro directed differentiation of mouse embryonic stem cells into insulin-producing cells. Diabetologia 47:1442–1451. https://doi.org/10.1007/s00125-004-1458-8
Li Z Rana TM (2012) Using microRNAs to enhance the generation of induced pluripotent stem cells. Curr Protocols Stem Cell Biol 20(1):4D-4. https://doi.org/10.1002/9780470151808.sc04a04s20
Li H-T, Jiang F-X, Shi P, Zhang T, Liu X-Y, Lin X-W, Pang X-N (2012) In vitro reprogramming of rat bone marrow-derived mesenchymal stem cells into insulin-producing cells by genetically manipulating negative and positive regulators. Biochem Biophys Res Commun 420(4):793–798. https://doi.org/10.1016/j.bbrc.2012.03.076
Li N, Douko J, Qian H, Fei H et al (2020) microRNA-181c-5p promotes the formation of insulin-producing cells from human induced pluripotent stem cells by targeting smad7 and TGIF2. Cell Death Dis 11:462. https://doi.org/10.1038/s41419-020-2668-9
Lima MJ, Muir KR, Docherty HM, McGowan NWA, Forbes S, Heremans Y, Heimberg H et al (2016) Generation of functional beta-like cells from human exocrine pancreas. PLoS One 11(5):e0156204. https://doi.org/10.1371/journal.pone.0156204
Limbert C, Path G, Ebert R, Rothhammer V, Kassem M, Jakob F, Seufert J (2011) Pdx1- and ngn3-mediated in vitro reprogramming of human bone marrow-derived mesenchymal stromal cells into pancreatic endocrine lineages. Cytotherapy 13:802–813. https://doi.org/10.3109/14653249.2011.571248
Lin Y-C, Li Y-J, Rui Y-F, Dai G-C, Shi L, Xu H-L, Ni M, Zhao S, Chen H, Wang C, Li G, Teng G-J (2017) The effects of high glucose on tendon-derived stem cells: implications of the pathogenesis of diabetic tendon disorders. Oncotarget 8(11):17518. https://doi.org/10.18632/oncotarget.15418
Liu L, Yu Q, Lin J, Lai X, Cao W, Du K, Wang Y, Wu K, Hu Y, Zhang L, **ao H, Duan Y, Huang H (2011) Hypoxia-inducible factor-1alpha is essential for hypoxia-induced mesenchymal stem cell mobilization into the peripheral blood. Stem Cells Dev 20:1961–1971. https://doi.org/10.1089/scd.2010.0453
Liu Y, Li Z, Liu T, Xue X, Jiang H, Huang J, Wang H (2013) Impaired cardioprotective function of transplantation of mesenchymal stem cells from patients with diabetes mellitus to rats with experimentally induced myocardial infarction. Cardiovasc Diabetol 12:40. http://www.cardiab.com/content/12/1/40
Lopez-Talavera JC, Garcia-Ocana A, Sipula I, Takane KK, Cozar-Castellano I, Stewart AF (2004) Hepatocyte growth factor gene therapy for pancreatic islets in diabetes: reducing the minimal islet transplant mass required in a glucocorticoid-free rat model of allogeneic portal vein islet transplantation. Endocrinology 145:467–474. https://doi.org/10.1210/en.2003-1070
Lu G, Haider HK, Porollo A, Ashraf M (2010) Mitochondria-specific transgenic overexpression of connexin-43 simulates preconditioning-induced cytoprotection of stem cells. Cardiovasc Res 88(2):277–286. https://doi.org/10.1093/cvr/cvq293
Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292:1389–1394. https://doi.org/10.1126/science.1058866
Ma J-H, Su LP, Zhu J, Law PK, Lee K-O, Lei Y, Wang Z-Z (2013) Skeletal myoblast transplantation on gene expression profiles of insulin signaling pathway and mitochondrial biogenesis and function in skeletal muscle. Diabetes Res Clin Pract 102(1):43–52. https://doi.org/10.1016/j.diabres.2013.08.006
Mabed M, Shahin M (2012) Mesenchymal stem cell-based therapy for the treatment of type 1 diabetes mellitus. Curr Stem Cell Res Ther 7:179–190. https://doi.org/10.2174/157488812799859829
Martinez-Fernandez A, Nelson TJ, Ikeda Y, Terzic A (2010) C-myc independent nuclear reprogramming favors cardiogenic potential of induced pluripotent stem cells. J Cardiovasc Transl Res 3:13–23. https://doi.org/10.1007/s12265-009-9150-5
Martinez-Sanchez A, Rutter GA, Latreille M (2017) MiRNAs in β-cell development, identity, and disease. Front Genet 7:226. https://doi.org/10.3389/fgene.2016.00226
Maxwell GK, Punn A, Leonardo V-C, Kim HM, Rei A, Hogrebe NJ, Shuntaro M, Fumihko U, Jefferey MR (2020) Gene-edited human stem cell–derived β cells from a patient with monogenic diabetes reverse preexisting diabetes in mice. Sci Transl Med 12(540):eaax9106. https://doi.org/10.1126/scitranslmed.aax9106
McGrath PS, Diette N, Kogut I, Bilousova G (2018) RNA-based reprogramming of human primary fibroblasts into induced pluripotent stem cells. JoVE (J Visual Exp) 141:e58687. https://doi.org/10.3791/58687
McKimpson WM, Accili D (2019) Reprogramming cells to make insulin. J Endocrine Soc 3(6):1214–1226. https://doi.org/10.1210/js.2019-00040
Meng S, Cao J-T, Zhang B, Zhou Q, Shen C-X, Wang C-Q (2012) Downregulation of microRNA-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene Spred-1. J Mol Cell Cardiol 53(1):64–72. https://doi.org/10.1016/j.yjmcc.2012.04.003
Molgat, André SD, Tilokee EL, Rafatian G, Vulesevic B, Ruel M, Milne R, Suuronen EJ, Davis DR (2014) Hyperglycemia inhibits cardiac stem cell–mediated cardiac repair and angiogenic capacity. Circulation 130(11_suppl_1):S70–S76. https://doi.org/10.1161/CIRCULATIONAHA
Montagud-Marrahi E, Molina-Andújar A, Pané A, Ramírez-Bajo MJ, Amor A, Esmatjes E, Ferrer J et al (2020) Outcomes of pancreas transplantation in older diabetic patients. BMJ Open Diabetes Res Care 8(1):e000916. https://doi.org/10.1136/bmjdrc-2019-000916
Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S (2008) Generation of induced pluripotent stem cells without myc from mouse and human fibroblasts. Nat Biotechnol 26:101–106. https://doi.org/10.1038/nbt1374
Neef K, Choi YH, Weichel A, Rahmanian PB, Liakopoulos OJ, Stamm C, Choi CY, Jacobshagen C, Wittwer T, Wahlers T (2012) The influence of cardiovascular risk factors on bone marrow mesenchymal stromal cell fitness. Cytotherapy 14:670–678
Neshati Z, Matin MM, Bahrami AR, Moghimi A (2010) Differentiation of mesenchymal stem cells to insulin-producing cells and their impact on type 1 diabetic rats. J Physiol Biochem 66:181–187. https://doi.org/10.1007/s13105-010-0013-y
Ngoc PK, Phuc PV, Nhung TH, Thuy DT, Nguyet NT (2011) Improving the efficacy of type 1 diabetes therapy by transplantation of immunoisolated insulin-producing cells. Hum Cell 24:86–95. https://doi.org/10.1007/s13577-011-0018-z
Noiseux N, Borie M, Desnoyers A, Menaouar A, Stevens LM, Mansour S, Danalache BA, Roy DC, Jankowski M, Gutkowska J (2012) Preconditioning of stem cells by oxytocin to improve their therapeutic potential. Endocrinology 153:5361–5372. https://doi.org/10.1210/en.2012-1402
Oh SH, Muzzonigro TM, Bae SH, LaPlante JM, Hatch HM, Petersen BE (2004) Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type i diabetes. Lab Investig 84:607–617. https://doi.org/10.1038/labinvest.3700074
Oh YS, Shin S, Lee Y-J, Kim EH, Jun H-S (2011) Betacellulin-induced beta cell proliferation and regeneration is mediated by activation of ErbB-1 and ErbB-2 receptors. PLoS One 6(8):e23894. https://doi.org/10.1371/journal.pone.0023894
Ohmine S, Squillace KA, Hartjes KA, Deeds MC, Armstrong AS, Thatava T, Sakuma T, Terzic A, Kudva Y, Ikeda Y (2012) Reprogrammed keratinocytes from elderly type 2 diabetes patients suppress senescence genes to acquire induced pluripotency. Aging (Albany NY) 4:60–73. https://doi.org/10.18632/aging.100428
Ohnishi S, Sumiyoshi H, Kitamura S, Nagaya N (2007) Mesenchymal stem cells attenuate cardiac fibroblast proliferation and collagen synthesis through paracrine actions. FEBS Lett 581:3961–3966. https://doi.org/10.1016/j.febslet.2007.07.028
Oikawa A, Siragusa M, Quaini F, Mangialardi G, Katare RG, Caporali A, Van Buul JD, van Alphen FP, Graiani G et al (2010) Diabetes mellitus induces bone marrow microangiopathy. Arterioscler Thromb Vasc Biol 30(3):498–508. https://doi.org/10.1161/ATVBAHA.109.200154
Okawa T, Kamiya H, Himeno T, Kato J, Seino Y, Fujiya A, Kondo M et al (2013) Transplantation of neural crest like cells derived from induced pluripotent stem cells improves diabetic polyneuropathy in mice. Cell Transplant 22(10):1767–1783. https://doi.org/10.3727/096368912X657710
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. https://doi.org/10.1126/science.1164270
Om PG, Segal A, Blair E, Beaser R, Gaglia J, Halprin E, Gabbay RA, the members of the Joslin Clinical Oversight Committee (2018) CHAPTER 5. Clinical guideline for pharmacological management of adults with type 2 diabetes. Am J Manag Care 24(7):SP253–SO262
Ou Z, Niu X, He W, Chen Y, Song B, **an Y, Fan D, Tang D et al (2016) The combination of CRISPR/Cas9 and iPSC technologies in the gene therapy of human β-thalassemia in mice. Sci Rep 6:32463. https://doi.org/10.1038/srep32463
Ozdemir M, Attar A, Kuzu I, Ayten M, Ozgencil E, Bozkurt M, Dalva K, Uckan D, Kilic E, Sancak T, Kanpolat Y, Beksac M (2012) Stem cell therapy in spinal cord injury: In vivo and postmortem tracking of bone marrow mononuclear or mesenchymal stem cells. Stem Cell Rev 8:953–962. https://doi.org/10.1007/s12015-012-9376-5
Park HY, Noh EH, Chung HM, Kang MJ, Kim EY, Park SP (2012) Efficient generation of virus-free ips cells using liposomal magnetofection. PLoS One 7:e45812. https://doi.org/10.1371/journal.pone.0045812
Paz AH, Salton GD, Ayala-Lugo A, Gomes C, Terraciano P, Scalco R, Laurino CC et al (2011) Betacellulin overexpression in mesenchymal stem cells induces insulin secretion in vitro and ameliorates streptozotocin-induced hyperglycemia in rats. Stem Cells Dev 20:223–232. https://doi.org/10.1089/scd.2009.0490
Perrera V, Martello G (2019) How does reprogramming to pluripotency affect genomic imprinting? Front Cell Dev Biol 7:76. https://doi.org/10.3389/fcell.2019.00076
Phadnis SM, Joglekar MV, Dalvi MP, Muthyala S, Nair PD, Ghaskadbi SM, Bhonde RR, Hardikar AA (2011) Human bone marrow-derived mesenchymal cells differentiate and mature into endocrine pancreatic lineage in vivo. Cytotherapy 13(3):279–293. https://doi.org/10.3109/14653249.2010.523108
Piero MN, Nzaro GM, Njagi JM (2015) Diabetes mellitus-a devastating metabolic disorder. Asian J Biomed Pharm Sci 5(40):1. https://doi.org/10.15272/ajbps.v4i40.645
Piyaporn R, Dechsukhum C, Leeanansaksiri W (2018) Establishment of insulin-producing cells from human embryonic stem cells underhypoxic condition for cell based therapy. Front Cell Dev Biol 6:49. https://doi.org/10.3389/fcell.2018.00049
Poljak-Blazi M, Slijepcevic M, Boranic M (1980) Cfus reduction and adaptation in mice with experimental diabetes. Exp Hematol 8:174–178. PMID: 7009182
Polouliakh N (2013) Reprogramming resistant genes: In-depth comparison of gene expressions among ips, es, and somatic cells. Front Physiol 4:7. https://doi.org/10.3389/fphys.2013.00007
Prabakar KR, Dominguez-Bendala J, Molano RD, Pileggi A, Villate S, Ricordi C, Inverardi L (2012) Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells. Cell Transplant 21:1321–1339. https://doi.org/10.3727/096368911X612530
Puri S, Roy N, Russ HA, Leonhardt L, French EK, Roy R, Bengtsson H et al (2018) Replication confers β cell immaturity. Nat Commun 9(1):1–12. https://doi.org/10.1038/s41467-018-02939-0
Qi L, Ahmadi AR, Huang J, Chen M, Pan B, Kuwabara H, Iwasaki K et al (2020) Major improvement in wound healing through pharmacologic mobilization of stem cells in severely diabetic rats. Diabetes 69(4):699–712
Rahim F, Arjmand B, Shirbandi K, Payab M, Larijani B (2018) Stem cell therapy for patients with diabetes: a systematic review and meta-analysis of metabolomics-based risks and benefits. Stem Cell Investig 5:40. https://doi.org/10.21037/sci.2018.11.01
Raikwar SP, Zavazava N (2012) Pdx1-engineered embryonic stem cell-derived insulin producing cells regulate hyperglycemia in diabetic mice. Transplant Res 1:19. https://doi.org/10.1186/2047-1440-1-19
Raikwar SP, Kim E-M, William I, Allamargot SC, Thedens DR, Zavazava N (2015) Human iPS cell-derived insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice. PLoS One 10(1):e0116582. https://doi.org/10.1371/journal.pone.0116582
Rajab A, Rahman S, Rajab TM, Haider HK (2018) Morphology and chromic status of red blood cells are significantly influenced by gestational diabetes. J Hematol 7(4):140. https://doi.org/10.14740/jh449w
Rattananinsruang P, Dechsukhum C, Leeanansaksiri W (2018) Establishment of Insulin-Producing Cells From Human Embryonic Stem Cells Underhypoxic Condition for Cell Based Therapy. Front Cell Dev Biol 6:49. https://doi.org/10.3389/fcell.2018.00049
Rawal S, Munasinghe PE, Shindikar A, Paulin J, Cameron V, Manning P, Williams MJ (2017) Down-regulation of proangiogenic microRNA-126 and microRNA-132 are early modulators of diabetic cardiac microangiopathy. Cardiovasc Res 113(1):90–101. https://doi.org/10.1093/cvr/cvw235
Reyhaneh NM, Fatemeh S, Mohamad AF, Sepehr T, Abdolreza A, Pegah G, Ahmad MS et al (2018) Collagen coated electrospun polyethersulfone nanofibers improved insulin producing cells differentiation potential of human induced pluripotent stem cells. Artif Cells Nanomed Biotechnol 46(3):S734–S739. https://doi.org/10.1080/21691401.2018.1508031
Rezania A, Bruin JE, Riedel MJ, Mojibian M, Asadi A, Xu J, Gauvin R, Narayan K, Karanu F, O’Neil JJ, Ao Z, Warnock GL, Kieffer TJ (2012) Maturation of human embryonic stem cell-derived pancreatic progenitors into functional islets capable of treating pre-existing diabetes in mice. Diabetes 61:2016–2029. https://doi.org/10.2337/db11-1711
Robitaille K, Rourke JL, McBane JE, Fu A, Baird S, Du Q, Kin T, Shapiro AMJ, Screaton RA (2016) High-throughput functional genomics identifies regulators of primary human beta cell proliferation. J Biol Chem 291(9):4614–4625. https://doi.org/10.1074/jbc.M115.683912
Rodrigues M, Wong VW, Rennert RC, Davis CR, Longaker MT, Gurtner GC (2015) Progenitor cell dysfunctions underlie some diabetic complications. Am J Pathol 185(10):2607–2618. https://doi.org/10.1016/j.ajpath.2015.05.003
Russ HA, Parent AV, Ringler JJ, Hennings TG, Nair GG, Shveygert M, Guo T, Puri S et al (2015) Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. EMBO J 34(13):1759–1772. https://doi.org/10.15252/embj.201591058
Salg GA, Giese NA, Schenk M, Hüttner FJ, Felix K, Probst P, Diener MK, Hackert T, Kenngott HG (2019) The emerging field of pancreatic tissue engineering: a systematic review and evidence map of scaffold materials and scaffolding techniques for insulin-secreting cells. J Tissue Eng 10:2041731419884708. https://doi.org/10.1177/2041731419884708
Santamaria X, Massasa EE, Feng Y, Wolff E, Taylor HS (2011) Derivation of insulin producing cells from human endometrial stromal stem cells and use in the treatment of murine diabetes. Mol Ther 19:2065–2071. https://doi.org/10.1038/mt.2011.173
Sassoli C, Pini A, Chellini F, Mazzanti B, Nistri S, Nosi D, Saccardi R, Quercioli F, Zecchi-Orlandini S, Formigli L (2012) Bone marrow mesenchymal stromal cells stimulate skeletal myoblast proliferation through the paracrine release of vegf. PLoS One 7:e37512. https://doi.org/10.1371/journal.pone.0037512
Sattar N (2019) Advances in the clinical management of type 2 diabetes: a brief history of the past 15 years and challenges for the future. BMC Med 17(1):1–4. https://doi.org/10.1186/s12916-019-1281-1
Schulz TC, Young HY, Agulnick AD, Babin MJ, Baetge EE, Bang AG, Bhoumik A et al (2012) A scalable system for production of functional pancreatic progenitors from human embryonic stem cells. PLoS One 7:e37004. https://doi.org/10.1371/journal.pone.0037004
Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D (2004) Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 22(9):1115–1124. https://doi.org/10.1038/nbt1004
Shaer AS, Azarpira N, Karimi MH (2014) Differentiation of human induced pluripotent stem cells into insulin-like cell clusters with miR-186 and miR-375 by using chemical transfection. Appl Biochem Biotechnol 174(1):242–258. https://doi.org/10.1007/s12010-014-1045-5
Shahjalal HM, Shiraki N, Sakano D, Kikawa K, Ogaki S, Baba H, Kume K, Kume S (2014) Generation of insulin-producing beta-like cells from human ips cells in a defined and completely xeno-free culture system. J Mol Cell Biol 6(5):394–408. https://doi.org/10.1093/jmcb/mju029
Shahjalal HM, Dayem AA, Lim KM, Jeon T-I, Cho S-G (2018) Generation of pancreatic β cells for treatment of diabetes: advances and challenges. Stem Cell Res Ther 9(1):355. https://doi.org/10.1186/s13287-018-1099-3
Shen W, Taylor B, ** Q, Nguyen-Tran V, Meeusen S, Zhang Y-Q, Kamireddy A et al (2015) Inhibition of DYRK1A and GSK3B induces human β-cell proliferation. Nat Commun 6(1):1–11. https://doi.org/10.1038/ncomms9372
Shin L, Peterson D (2012) Impaired therapeutic capacity of autologous stem cells in a model of type 2 diabetes. Stem Cells Transl Med 1(2):125–135. https://doi.org/10.5966/sctm.2012-0031
Shirakawa J, Kulkarni RN (2016) Novel factors modulating human β-cell proliferation. Diabetes Obes Metab 18 Suppl 1(Suppl 1):71–77. https://doi.org/10.1111/dom.12731
Shruti R, Munasinghe PE, Shindikar A, Paulin J, Cameron V, Manning P, Williams MJA et al (2017) Down-regulation of proangiogenic microRNA-126 and microRNA-132 are early modulators of diabetic cardiac microangiopathy. Cardiovasc Res 113(1):90–101. https://doi.org/10.1093/cvr/cvw235
Shuen-ing T, Zeng C, Field L, Dhawan S, Bhushan A, Georgia S (2017) Cyclin D2 is sufficient to drive β cell self-renewal and regeneration. Cell Cycle 16(22):2183–2191. https://doi.org/10.1080/15384101.2017.1319999
Si Y, Zhao Y, Hao H, Liu J, Guo Y, Mu Y, Shen J et al (2012) Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity. Diabetes 61(6):1616–1625. https://doi.org/10.2337/db11-1141
Si-Tayeb K, Noto FK, Sepac A, Sedlic F, Bosnjak ZJ, Lough JW, Duncan SA (2010) Generation of human induced pluripotent stem cells by simple transient transfection of plasmid DNA encoding reprogramming factors. BMC Dev Biol 10(1):81. https://doi.org/10.1186/1471-213X-10-81
Smukler SR, Arntfield ME, Razavi R, Bikopoulos G, Karpowicz P, Seaberg R, Dai F, Lee S, Ahrens R, Fraser PE, Wheeler MB, van der Kooy D (2011) The adult mouse and human pancreas contain rare multipotent stem cells that express insulin. Cell Stem Cell 8:281–293. https://doi.org/10.1016/j.stem.2011.01.015
Soria B (2001) In-vitro differentiation of pancreatic β-cells. Differentiation 68(4–5):205–219. https://doi.org/10.1046/j.1432-0436.2001.680408.x
Soria B, Roche E, Berná G, León-Quinto T, Reig JA, Martín F (2000) Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49(2):157–162. https://doi.org/10.2337/diabetes.49.2.157
Spagnoli FM (2018) Location matters for insulin-producing cells. Nature 564:50–51. https://doi.org/10.1038/d41586-018-07490-y
Srivastava A, Dadheech N, Vakani M, Gupta S (2019) Pancreatic resident endocrine progenitors demonstrate high islet neogenic fidelity and committed homing towards diabetic mice pancreas. J Cell Physiol 234(6):8975–8987. https://doi.org/10.1002/jcp.27568
Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (2008) Induced pluripotent stem cells generated without viral integration. Science 322:945–949. https://doi.org/10.1126/science.1162494
Stolzing A, Sellers D, Llewelyn O, Scutt A (2010) Diabetes induced changes in rat mesenchymal stem cells. Cells Tissues Organs 191:453–465. https://doi.org/10.1159/000281826
Sumi S (2011) Regenerative medicine for insulin deficiency: creation of pancreatic islets and bioartificial pancreas. J Hepato-Biliary-Pancreatic Sci 18(1):6–12. https://doi.org/10.1007/s00534-010-0303-3
Sun NZ, Ji HS (2009) In vitro differentiation of human placenta-derived adherent cells into insulin-producing cells. J Int Med Res 37:400–406. https://doi.org/10.1177/147323000903700215
Surrati A, Haider HKh (2019) Non-destructive metabolomics characterization of mesenchymal stem cell differentiation. In: Husnain Haider Kh (ed) Stem cells: from hype to hope. World Scientific, Singapore, pp 51–84
Suzuki Y, Kim HW, Ashraf M, Haider H (2010) Diazoxide potentiates mesenchymal stem cell survival via nf-kappab-dependent mir-146a expression by targeting fas. Am J Physiol Heart Circ Physiol 299:H1077–H1082. https://doi.org/10.1152/ajpheart.00212.2010
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. https://doi.org/10.1016/j.cell.2007.11.019
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(5):861–72. https://doi.org/10.1016/j.cell.2007.11.019
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:e25265. https://doi.org/10.1371/journal.pone.0025265
Taneera J, Rosengren A, Renstrom E, Nygren JM, Serup P, Rorsman P et al (2006) Failure of transplanted bone marrow cells to adopt a pancreatic β-cell fate. Diabetes 55(2):290–296. https://doi.org/10.2337/diabetes.55.02.06.db05-1212
Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR, Levine JP et al (2002) Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106(22):2781–2786. https://doi.org/10.1161/01.CIR.0000039526.42991.93
Thakur G, Lee H-J, Jeon R-H, Lee S-L, Rho G-J (2020) Small molecule-induced pancreatic β-like cell development: mechanistic approaches and available strategies. Int J Mol Sci 21(7):2388. https://doi.org/10.3390/ijms21072388
Thatava T, Nelson TJ, Edukulla R, Sakuma T, Ohmine S, Tonne JM, Yamada S, Kudva Y, Terzic A, Ikeda Y (2011) Indolactam v/glp-1-mediated differentiation of human ips cells into glucose-responsive insulin-secreting progeny. Gene Ther 18:283–293. https://doi.org/10.1038/gt.2010.145
Tomei AA, Villa C, Ricordi C (2015) Development of an encapsulated stem cell-based therapy for diabetes. Expert Opin Biol Ther 15(9):1321–1336. https://doi.org/10.1517/14712598.2015.1055242
Tsai PJ, Wang HS, Shyr YM, Weng ZC, Tai LC, Shyu JF, Chen TH (2012) Transplantation of insulin-producing cells from umbilical cord mesenchymal stem cells for the treatment of streptozotocin-induced diabetic rats. J Biomed Sci 19:47. https://doi.org/10.1186/1423-0127-19-47
Tuch BE, Gao SY, Lees JG (2014) Scaffolds for islets and stem cells differentiated into insulin-secreting cells. Front Biosci (Landmark Ed) 19:126–138
Unniappan S, Wideman RD, Donald C, Gunn V, Wall JL, Zhang QX, Webber TD, Cheung AT, Kieffer TJ (2009) Treatment of diabetes by transplantation of drug-inducible insulin-producing gut cells. J Mol Med (Berl) 87:703–712. https://doi.org/10.1007/s00109-0090465-0
van der Torren CR, Zaldumbide A, Duinkerken G, Brand-Schaaf SH, Peakman M, Stangé G, Martinson L et al (2017) Immunogenicity of human embryonic stem cell-derived beta cells. Diabetologia 60(1):126–133. https://doi.org/10.1007/s00125-016-4125-y
Veronesi F, Giavaresi G, Tschon M, Borsari V, Nicoli Aldini N, Fini M (2013) Clinical use of bone marrow, bone marrow concentrate, and expanded bone marrow mesenchymal stem cells in cartilage disease. Stem Cells Dev 22(2):181–192. https://doi.org/10.1089/scd.2012.0373
Vishnubalaji R, Manikandan M, Al-Nbaheen M, Kadalmani B, Aldahmash A, Alajez NM (2012) In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells. BMC Dev Biol 12(1):7. https://doi.org/10.1186/1471-213X-12-7
Wan S, Zhang J, Chen X, Lang J, Chen LF, Tian L, Meng Y et al (2020) MicroRNA-17-92 regulates beta-cell restoration after streptozotocin treatment. Front Endocrinol 11:9. https://doi.org/10.3389/fendo.2020.00009
Wang L, Liub T, Liang R, Wang G, Liu Y, Zou J, Liu N et al (2010) Mesenchymal stem cells ameliorate β cell dysfunction of human type-2 diabetic islets by reversing b cell dedifferentiation. EBioMedicine 51(102615):1–11. https://doi.org/10.1016/j.ebiom.2019.102615
Wang Q, Donelan W, Ye H, ** Y, Lin Y, Wu X, Wang Y et al (2019) Real-time observation of pancreatic beta cell differentiation from human induced pluripotent stem cells. Am J Transl Res 11(6):3490. PMCID: PMC6614661 PMID: 31312361
Wang L, Liu T, Liang R, Wang G, Liu Y, Zou J, Liu N et al (2020) Mesenchymal stem cells ameliorate β cell dysfunction of human type 2 diabetic islets by reversing β cell dedifferentiation. EBioMedicine 51:102615. https://doi.org/10.1016/j.ebiom.2019.102615
Watanabe A, Yamada Y, Yamanaka S (2013) Epigenetic regulation in pluripotent stem cells: a key to breaking the epigenetic barrier. Philos Trans R Soc B Biol Sci 368(1609):20120292. https://doi.org/10.1098/rstb.2012.0292
Wehbe T, Chahine NA, Sissi S, Abou-Joaude I, Chalhoub L (2016) Bone marrow derived stem cell therapy for type 2 diabetes mellitus. Stem Cell Investig 3. https://doi.org/10.21037/sci.2016.11.14
Wu H, Lu W, Mahato RI (2011) Mesenchymal stem cells as a gene delivery vehicle for successful islet transplantation. Pharm Res 28:2098–2109. https://doi.org/10.1007/s11095-011-0434-5
Wu L, Cai X, Zhang S, Karperien M, Lin Y (2013) Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine. J Cell Physiol 228(5):938–944. https://doi.org/10.1002/jcp.24255
**n Y, Jiang X, Wang Y, Su X, Sun M, Zhang L, Tan Y et al (2016) Insulin-producing cells differentiated from human bone marrow mesenchymal stem cells in vitro ameliorate streptozotocin-induced diabetic hyperglycaemia. PLoS One 11(1):e0145838. https://doi.org/10.1371/journal.pone.0145838
Xu B, Fan D, Zhao Y, Li J, Wang Z, Wang J, Wang X et al (2019a) Three-dimensional culture promotes the differentiation of human dental pulp mesenchymal stem cells into insulin-producing cells for improving the diabetes therapy. Front Pharmacol 10. https://doi.org/10.3389/fphar.2019.01576
Xu Y, Huang Y, Guo Y, **ong Y, Zhu S, Xu L, Lu J et al (2019b) microRNA-690 regulates induced pluripotent stem cells (iPSCs) differentiation into insulin-producing cells by targeting Sox9. Stem Cell Res Ther 10(1):1–13. https://doi.org/10.1186/s13287-019-1154-8
Yagi H, Soto-Gutierrez A, Parekkadan B, Kitagawa Y, Tompkins RG, Kobayashi N, Yarmush ML (2010) Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant 19:667–679. https://doi.org/10.3727/096368910X508762
Yan F, Yao Y, Chen L, Li Y, Sheng Z, Ma G (2012) Hypoxic preconditioning improves survival of cardiac progenitor cells: role of stromal cell derived factor-1alpha-cxcr4 axis. PLoS One 7:e37948. https://doi.org/10.1371/journal.pone.0037948
Yang G, Jia Y, Li C, Cheng Q, Yue W, Pei X (2015) Hyperglycemic stress impairs the stemness capacity of kidney stem cells in rats. PLoS One 10(10):e0139607. https://doi.org/10.1371/journal.pone.0139607
Yau TM, Pagani FD, Mancini DM, Chang HL, Woo J, Acker MA, Selzman CH, Soltesz EG et al (2019) Intramyocardial injection of mesenchymal precursor cells and successful temporary weaning from left ventricular assist device support in patients with advanced heart failure: a randomized clinical trial. JAMA 321(12):1176–1186. https://doi.org/10.1001/jama.2019.2341
Yechoor V, Liu V, Paul A, Lee J, Buras E, Ozer K, Samson S, Chan L (2009) Gene therapy with neurogenin 3 and betacellulin reverses major metabolic problems in insulin-deficient diabetic mice. Endocrinology 150:4863–4873. https://doi.org/10.1210/en.2009-0527
Yeung TY, Seeberger KL, Kin T, Adesida A, Jomha N, Shapiro AM, Korbutt GS (2012) Human mesenchymal stem cells protect human islets from pro-inflammatory cytokines. PLoS One 7:e38189. https://doi.org/10.1371/journal.pone.0038189
Zanini C, Bruno S, Mandili G, Baci D, Cerutti F, Cenacchi G, Izzi L, Camussi G, Forni M (2011) Differentiation of mesenchymal stem cells derived from pancreatic islets and bone marrow into islet-like cell phenotype. PLoS One 6:e28175. https://doi.org/10.1371/journal.pone.0028175
Zhang D, Jiang W, Liu M, Sui X, Yin X, Chen S, Shi Y, Deng H (2009a) Highly efficient differentiation of human es cells and ips cells into mature pancreatic insulin-producing cells. Cell Res 19:429–438. https://doi.org/10.1038/cr.2009.28
Zhang YH, Wang HF, Liu W, Wei B, Bing LJ, Gao YM (2009b) Insulin-producing cells derived from rat bone marrow and their autologous transplantation in the duodenal wall for treating diabetes. Anat Rec (Hoboken) 292:728–735. https://doi.org/10.1002/ar.20892
Zhang J, Kasim V, **e Y-D, Huang C, Sisjayawan J, Agne AD, Yan X-S, Wu X-Y, Liu C-P, Yang L, Miyagishi M, Wu S-R (2017) Inhibition of PHD3 by salidroside promotes neovascularization through cell–cell communications mediated by muscle-secreted angiogenic factors. Sci Rep 7:43935. https://doi.org/10.1038/srep43935
Zhang X, Meng K, Pu Y, Wang C, Chen Y, Wang L (2018) Hyperglycemia altered the fate of cardiac stem cells to adipogenesis through inhibiting the β-catenin/TCF-4 pathway. Cell Physiol Biochem 49(6):2254–2263. https://doi.org/10.1159/000493828
Zhong F, Jiang Y (2019) Endogenous pancreatic β cell regeneration: a potential strategy for the recovery of β cell deficiency in diabetes. Front Endocrinol 10:101
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Kh, S., Haider, K.H. (2021). Stem Cells: A Renewable Source of Pancreatic β-Cells and Future for Diabetes Treatment. In: Haider, K.H. (eds) Stem Cells. Springer, Cham. https://doi.org/10.1007/978-3-030-77052-5_12
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