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Bone marrow derived stem cells in joint and bone diseases: a concise review

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Abstract

Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients’ life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a “reservoir” of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called “stem cell niche” was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the treatment of bone, cartilage and meniscus tissues.

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References

  1. Ivkovic A, Marijanovic I, Hudetz D et al (2011) Regenerative medicine and tissue engineering in orthopaedic surgery. Front Biosci (Elite Ed) 3:923–944

    Google Scholar 

  2. Hoffmann A, Gross G (2007) Tendon and ligament engineering in the adult organism: mesenchymal stem cells and gene-therapeutic approaches. Int Orthop 31:791–797. doi:10.1007/s00264-007-0395-9

    PubMed Central  PubMed  Google Scholar 

  3. Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317. doi:10.1080/14653240600855905

    CAS  PubMed  Google Scholar 

  4. Brown PT, Squire MW, Li W-J (2014) Characterization and evaluation of mesenchymal stem cells derived from human embryonic stem cells and bone marrow. Cell Tissue Res. doi:10.1007/s00441-014-1926-5

    PubMed  Google Scholar 

  5. Lin C-S, **n Z-C, Dai J, Lue TF (2013) Commonly used mesenchymal stem cell markers and tracking labels: limitations and challenges. Histol Histopathol 28:1109–1116

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Beitzel K, McCarthy MB, Cote MP et al (2014) Properties of biologic scaffolds and their response to mesenchymal stem cells. Arthroscopy 30:289–298. doi:10.1016/j.arthro.2013.11.020

    PubMed  Google Scholar 

  7. Watson JT, Foo T, Wu J et al (2013) CD271 as a marker for mesenchymal stem cells in bone marrow versus umbilical cord blood. Cells Tissues Organs (Print) 197:496–504. doi:10.1159/000348794

    CAS  Google Scholar 

  8. Hermida-Gómez T, Fuentes-Boquete I, Gimeno-Longas MJ et al (2011) Bone marrow cells immunomagnetically selected for CD271+ antigen promote in vitro the repair of articular cartilage defects. Tissue Eng Part A 17:1169–1179. doi:10.1089/ten.TEA.2010.0346

    PubMed  Google Scholar 

  9. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    CAS  PubMed  Google Scholar 

  10. Caplan AI, Bruder SP (2001) Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends Mol Med 7:259–264

    CAS  PubMed  Google Scholar 

  11. Sousa BR, Parreira RC, Fonseca EA et al (2014) Human adult stem cells from diverse origins: an overview from multiparametric immunophenoty** to clinical applications. Cytom A 85:43–77. doi:10.1002/cyto.a.22402

    Google Scholar 

  12. Gates CB, Karthikeyan T, Fu F, Huard J (2008) Regenerative medicine for the musculoskeletal system based on muscle-derived stem cells. J Am Acad Orthop Surg 16:68–76

    PubMed  Google Scholar 

  13. Nohmi S, Yamamoto Y, Mizukami H et al (2012) Post injury changes in the properties of mesenchymal stem cells derived from human anterior cruciate ligaments. Int Orthop 36:1515–1522. doi:10.1007/s00264-012-1484-y

    PubMed Central  PubMed  Google Scholar 

  14. Rui YF, Lui PPY, Lee YW, Chan KM (2012) Higher BMP receptor expression and BMP-2-induced osteogenic differentiation in tendon-derived stem cells compared with bone-marrow-derived mesenchymal stem cells. Int Orthop 36:1099–1107. doi:10.1007/s00264-011-1417-1

    PubMed Central  PubMed  Google Scholar 

  15. Li H, Jiang J, Wu Y, Chen S (2012) Potential mechanisms of a periosteum patch as an effective and favourable approach to enhance tendon-bone healing in the human body. Int Orthop 36:665–669. doi:10.1007/s00264-011-1346-z

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Crisan M, Yap S, Casteilla L et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313. doi:10.1016/j.stem.2008.07.003

    CAS  PubMed  Google Scholar 

  17. Caplan AI, Correa D (2011) The MSC: an injury drugstore. Cell Stem Cell 9:11–15. doi:10.1016/j.stem.2011.06.008

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Collino F, Bruno S, Deregibus MC et al (2011) MicroRNAs and mesenchymal stem cells. Vitam Horm 87:291–320. doi:10.1016/B978-0-12-386015-6.00033-0

    CAS  PubMed  Google Scholar 

  19. Huang Q, Zhang H, Pei F et al (2010) Use of small interfering ribonucleic acids to inhibit the adipogenic effect of alcohol on human bone marrow-derived mesenchymal cells. Int Orthop 34:1059–1068. doi:10.1007/s00264-009-0914-y

    PubMed Central  PubMed  Google Scholar 

  20. Tsai M-T, Lin D-J, Huang S et al (2012) Osteogenic differentiation is synergistically influenced by osteoinductive treatment and direct cell-cell contact between murine osteoblasts and mesenchymal stem cells. Int Orthop 36:199–205. doi:10.1007/s00264-011-1259-x

    PubMed Central  PubMed  Google Scholar 

  21. Zuo Q, Cui W, Liu F et al (2013) Co-cultivated mesenchymal stem cells support chondrocytic differentiation of articular chondrocytes. Int Orthop 37:747–752. doi:10.1007/s00264-013-1782-z

    PubMed Central  PubMed  Google Scholar 

  22. Moioli EK, Clark PA, Chen M et al (2008) Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues. PLoS ONE 3:e3922. doi:10.1371/journal.pone.0003922

    PubMed Central  PubMed  Google Scholar 

  23. Chen JL, Hunt P, McElvain M et al (1997) Osteoblast precursor cells are found in CD34+ cells from human bone marrow. Stem Cells 15:368–377. doi:10.1002/stem.150368

    CAS  PubMed  Google Scholar 

  24. Ishida K, Matsumoto T, Sasaki K et al (2010) Bone regeneration properties of granulocyte colony-stimulating factor via neovascularization and osteogenesis. Tissue Eng Part A 16:3271–3284. doi:10.1089/ten.tea.2009.0268

    CAS  PubMed  Google Scholar 

  25. Mifune Y, Matsumoto T, Kawamoto A et al (2008) Local delivery of granulocyte colony stimulating factor-mobilized CD34-positive progenitor cells using bioscaffold for modality of unhealing bone fracture. Stem Cells 26:1395–1405. doi:10.1634/stemcells.2007-0820

    CAS  PubMed  Google Scholar 

  26. Kuroda R, Matsumoto T, Miwa M et al (2011) Local transplantation of G-CSF-mobilized CD34(+) cells in a patient with tibial nonunion: a case report. Cell Transplant 20:1491–1496. doi:10.3727/096368910X550189

    PubMed  Google Scholar 

  27. Saw K-Y, Anz A, Merican S et al (2011) Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology. Arthroscopy 27:493–506. doi:10.1016/j.arthro.2010.11.054

    PubMed  Google Scholar 

  28. Kasten P, Beyen I, Egermann M et al (2008) Instant stem cell therapy: characterization and concentration of human mesenchymal stem cells in vitro. Eur Cell Mater 16:47–55

    CAS  PubMed  Google Scholar 

  29. Horwitz EM, Prockop DJ, Fitzpatrick LA et al (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309–313. doi:10.1038/6529

    CAS  PubMed  Google Scholar 

  30. Götherström C, Westgren M, Shaw SWS et al (2013) Pre- and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience. Stem Cells Transl Med 3(2):255–264. doi:10.5966/sctm.2013-0090

    Google Scholar 

  31. Pauley P, Matthews BG, Wang L et al (2014) Local transplantation is an effective method for cell delivery in the osteogenesis imperfecta murine model. Int Orthop. doi:10.1007/s00264-013-2249-y

    PubMed  Google Scholar 

  32. Gangji V, De Maertelaer V, Hauzeur J-P (2011) Autologous bone marrow cell implantation in the treatment of non-traumatic osteonecrosis of the femoral head: Five year follow-up of a prospective controlled study. Bone 49:1005–1009. doi:10.1016/j.bone.2011.07.032

    PubMed  Google Scholar 

  33. Hernigou P, Poignard A, Zilber S, Rouard H (2009) Cell therapy of hip osteonecrosis with autologous bone marrow grafting. Indian J Orthop 43:40–45. doi:10.4103/0019-5413.45322

    PubMed Central  PubMed  Google Scholar 

  34. Hernigou P, Homma Y, Flouzat Lachaniette CH et al (2013) Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop 37:2279–2287. doi:10.1007/s00264-013-2017-z

    PubMed  Google Scholar 

  35. Gao Y-S, Zhang C-Q (2010) Cytotherapy of osteonecrosis of the femoral head: a mini review. Int Orthop 34:779–782. doi:10.1007/s00264-010-1009-5

    PubMed Central  PubMed  Google Scholar 

  36. Wen Q, Ma L, Chen Y-P et al (2008) Treatment of avascular necrosis of the femoral head by hepatocyte growth factor-transgenic bone marrow stromal stem cells. Gene Ther 15:1523–1535. doi:10.1038/gt.2008.110

    CAS  PubMed  Google Scholar 

  37. Wu X, Yang S, Duan D et al (2008) A combination of granulocyte colony-stimulating factor and stem cell factor ameliorates steroid-associated osteonecrosis in rabbits. J Rheumatol 35:2241–2248

    CAS  PubMed  Google Scholar 

  38. Le Nail L-R, Stanovici J, Fournier J et al (2014) Percutaneous grafting with bone marrow autologous concentrate for open tibia fractures: analysis of forty three cases and literature review. Int Orthop. doi:10.1007/s00264-014-2342-x

    PubMed  Google Scholar 

  39. Obermeyer TS, Yonick D, Lauing K et al (2012) Mesenchymal stem cells facilitate fracture repair in an alcohol-induced impaired healing model. J Orthop Trauma 26:712–718. doi:10.1097/BOT.0b013e3182724298

    PubMed Central  PubMed  Google Scholar 

  40. Granero-Moltó F, Weis JA, Miga MI et al (2009) Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells 27:1887–1898. doi:10.1002/stem.103

    PubMed Central  PubMed  Google Scholar 

  41. Fayaz HC, Giannoudis PV, Vrahas MS et al (2011) The role of stem cells in fracture healing and nonunion. Int Orthop 35:1587–1597. doi:10.1007/s00264-011-1338-z

    PubMed Central  PubMed  Google Scholar 

  42. Hernigou P, Poignard A, Beaujean F, Rouard H (2005) Percutaneous autologous bone-marrow grafting for nonunions. Influence of the number and concentration of progenitor cells. J Bone Joint Surg Am 87:1430–1437. doi:10.2106/JBJS.D.02215

    PubMed  Google Scholar 

  43. Hatzokos I, Stavridis SI, Iosifidou E et al (2011) Autologous bone marrow grafting combined with demineralized bone matrix improves consolidation of docking site after distraction osteogenesis. J Bone Joint Surg Am 93:671–678. doi:10.2106/JBJS.J.00514

    PubMed  Google Scholar 

  44. Giannotti S, Trombi L, Bottai V et al (2013) Use of autologous human mesenchymal stromal cell/fibrin clot constructs in upper limb non-unions: long-term assessment. PLoS ONE 8:e73893. doi:10.1371/journal.pone.0073893

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Jäger M, Jelinek EM, Wess KM et al (2009) Bone marrow concentrate: a novel strategy for bone defect treatment. Curr Stem Cell Res Ther 4:34–43

    PubMed  Google Scholar 

  46. Stiehler M, Seib FP, Rauh J et al (2010) Cancellous bone allograft seeded with human mesenchymal stromal cells: a potential good manufacturing practice-grade tool for the regeneration of bone defects. Cytotherapy 12:658–668. doi:10.3109/14653241003774052

    CAS  PubMed  Google Scholar 

  47. Nather A, David V, Teng JWH et al (2010) Effect of autologous mesenchymal stem cells on biological healing of allografts in critical-sized tibial defects simulated in adult rabbits. Ann Acad Med Singap 39:599–606

    PubMed  Google Scholar 

  48. Liu X, Li X, Fan Y et al (2010) Repairing goat tibia segmental bone defect using scaffold cultured with mesenchymal stem cells. J Biomed Mater Res Part B Appl Biomater 94:44–52. doi:10.1002/jbm.b.31622

    PubMed  Google Scholar 

  49. Omae H, Mochizuki Y, Yokoya S et al (2007) Augmentation of tendon attachment to porous ceramics by bone marrow stromal cells in a rabbit model. Int Orthop 31:353–358. doi:10.1007/s00264-006-0194-8

    PubMed Central  PubMed  Google Scholar 

  50. Yu Z, Zhu T, Li C et al (2012) Improvement of intertrochanteric bone quality in osteoporotic female rats after injection of polylactic acid-polyglycolic acid copolymer/collagen type I microspheres combined with bone mesenchymal stem cells. Int Orthop 36:2163–2171. doi:10.1007/s00264-012-1543-4

    PubMed Central  PubMed  Google Scholar 

  51. Daei-Farshbaf N, Ardeshirylajimi A, Seyedjafari E et al (2014) Bioceramic-collagen scaffolds loaded with human adipose-tissue derived stem cells for bone tissue engineering. Mol Biol Rep 41:741–749. doi:10.1007/s11033-013-2913-8

    CAS  PubMed  Google Scholar 

  52. Tang M, Chen W, Liu J et al (2014) Human induced pluripotent stem cell-derived mesenchymal stem cell seeding on calcium phosphate scaffold for bone regeneration. Tissue Eng Part A 20(7-8):1295–1305. doi:10.1089/ten.TEA.2013.0211

    Google Scholar 

  53. Gao C, Harvey EJ, Chua M et al (2013) MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects. Eur Cell Mater 26:195–207, discussion 207

    CAS  PubMed  Google Scholar 

  54. Wang X, Wang Y, Gou W et al (2013) Role of mesenchymal stem cells in bone regeneration and fracture repair: a review. Int Orthop 37:2491–2498. doi:10.1007/s00264-013-2059-2

    PubMed  Google Scholar 

  55. Pang H, Wu X-H, Fu S-L et al (2013) Prevascularisation with endothelial progenitor cells improved restoration of the architectural and functional properties of newly formed bone for bone reconstruction. Int Orthop 37:753–759. doi:10.1007/s00264-012-1751-y

    PubMed Central  PubMed  Google Scholar 

  56. Berner A, Pfaller C, Dienstknecht T et al (2011) Arthroplasty of the lunate using bone marrow mesenchymal stromal cells. Int Orthop 35:379–387. doi:10.1007/s00264-010-0997-5

    PubMed Central  PubMed  Google Scholar 

  57. Hao W, Dong J, Jiang M et al (2010) Enhanced bone formation in large segmental radial defects by combining adipose-derived stem cells expressing bone morphogenetic protein 2 with nHA/RHLC/PLA scaffold. Int Orthop 34:1341–1349. doi:10.1007/s00264-009-0946-3

    PubMed Central  PubMed  Google Scholar 

  58. Ozturk AM, Cila E, Kanatli U et al (2005) Treatment of segmental bone defects in rats by the stimulation of bone marrow osteo-progenitor cells with prostaglandin E2. Int Orthop 29:73–77. doi:10.1007/s00264-004-0623-5

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Hernigou P, Pariat J, Queinnec S et al (2014) Supercharging irradiated allografts with mesenchymal stem cells improves acetabular bone grafting in revision arthroplasty. Int Orthop. doi:10.1007/s00264-014-2285-2

    Google Scholar 

  60. Homma Y, Kaneko K, Hernigou P (2013) Supercharging allografts with mesenchymal stem cells in the operating room during hip revision. Int Orthop. doi:10.1007/s00264-013-2221-x

    Google Scholar 

  61. Marcacci M, Kon E, Moukhachev V et al (2007) Stem cells associated with macroporous bioceramics for long bone repair: 6- to 7-year outcome of a pilot clinical study. Tissue Eng 13:947–955. doi:10.1089/ten.2006.0271

    CAS  PubMed  Google Scholar 

  62. Zhi L, Chen C, Pang X et al (2011) Synergistic effect of recombinant human bone morphogenic protein-7 and osteogenic differentiation medium on human bone-marrow-derived mesenchymal stem cells in vitro. Int Orthop 35:1889–1895. doi:10.1007/s00264-011-1247-1

    PubMed Central  PubMed  Google Scholar 

  63. Grasser WA, Orlic I, Borovecki F et al (2007) BMP-6 exerts its osteoinductive effect through activation of IGF-I and EGF pathways. Int Orthop 31:759–765. doi:10.1007/s00264-007-0407-9

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Djapic T, Kusec V, Jelic M et al (2003) Compressed homologous cancellous bone and bone morphogenetic protein (BMP)-7 or bone marrow accelerate healing of long-bone critical defects. Int Orthop 27:326–330. doi:10.1007/s00264-003-0496-z

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Marmotti A, Castoldi F, Rossi R et al (2013) Bone marrow-derived cell mobilization by G-CSF to enhance osseointegration of bone substitute in high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc 21(1):237–248. doi:10.1007/s00167-012-2150-z

    Google Scholar 

  66. Dozza B, Di Bella C, Lucarelli E et al (2011) Mesenchymal stem cells and platelet lysate in fibrin or collagen scaffold promote non-cemented hip prosthesis integration. J Orthop Res 29:961–968. doi:10.1002/jor.21333

    CAS  PubMed  Google Scholar 

  67. Mueller MB, Fischer M, Zellner J et al (2013) Effect of parathyroid hormone-related protein in an in vitro hypertrophy model for mesenchymal stem cell chondrogenesis. Int Orthop 37:945–951. doi:10.1007/s00264-013-1800-1

    PubMed Central  PubMed  Google Scholar 

  68. Mueller MB, Blunk T, Appel B et al (2013) Insulin is essential for in vitro chondrogenesis of mesenchymal progenitor cells and influences chondrogenesis in a dose-dependent manner. Int Orthop 37:153–158. doi:10.1007/s00264-012-1726-z

    PubMed Central  PubMed  Google Scholar 

  69. Pecina M, Jelic M, Martinovic S et al (2002) Articular cartilage repair: the role of bone morphogenetic proteins. Int Orthop 26:131–136. doi:10.1007/s00264-002-0338-4

    CAS  PubMed Central  PubMed  Google Scholar 

  70. Pecina M, Vukicevic S (2007) Biological aspects of bone, cartilage and tendon regeneration. Int Orthop 31:719–720. doi:10.1007/s00264-007-0425-7

    PubMed Central  PubMed  Google Scholar 

  71. Borovecki F, Pecina-Slaus N, Vukicevic S (2007) Biological mechanisms of bone and cartilage remodelling–genomic perspective. Int Orthop 31:799–805. doi:10.1007/s00264-007-0408-8

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Vukicevic S, Oppermann H, Verbanac D et al (2013) The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing. Int Orthop 38(3):635–647. doi:10.1007/s00264-013-2201-1

    Google Scholar 

  73. Lee KBL, Hui JHP, Song IC et al (2007) Injectable mesenchymal stem cell therapy for large cartilage defects–a porcine model. Stem Cells 25:2964–2971. doi:10.1634/stemcells.2006-0311

    PubMed  Google Scholar 

  74. Agung M, Ochi M, Yanada S et al (2006) Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surg Sports Traumatol Arthrosc 14:1307–1314. doi:10.1007/s00167-006-0124-8

    PubMed  Google Scholar 

  75. Dowthwaite GP, Bishop JC, Redman SN et al (2004) The surface of articular cartilage contains a progenitor cell population. J Cell Sci 117:889–897. doi:10.1242/jcs.00912

    CAS  PubMed  Google Scholar 

  76. Yasuhara R, Ohta Y, Yuasa T et al (2011) Roles of β-catenin signaling in phenotypic expression and proliferation of articular cartilage superficial zone cells. Lab Invest 91:1739–1752. doi:10.1038/labinvest.2011.144

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Kurth TB, Dell’accio F, Crouch V et al (2011) Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo. Arthritis Rheum 63:1289–1300. doi:10.1002/art.30234

    PubMed  Google Scholar 

  78. Guo X, Zheng Q, Yang S et al (2006) Repair of full-thickness articular cartilage defects by cultured mesenchymal stem cells transfected with the transforming growth factor beta1 gene. Biomed Mater 1:206–215. doi:10.1088/1748-6041/1/4/006

    CAS  PubMed  Google Scholar 

  79. Cucchiarini M, Ekici M, Schetting S et al (2011) Metabolic activities and chondrogenic differentiation of human mesenchymal stem cells following recombinant adeno-associated virus-mediated gene transfer and overexpression of fibroblast growth factor 2. Tissue Eng Part A 17:1921–1933. doi:10.1089/ten.TEA.2011.0018

    CAS  PubMed  Google Scholar 

  80. Katayama R, Wakitani S, Tsumaki N et al (2004) Repair of articular cartilage defects in rabbits using CDMP1 gene-transfected autologous mesenchymal cells derived from bone marrow. Rheumatology (Oxford) 43:980–985. doi:10.1093/rheumatology/keh240

    CAS  Google Scholar 

  81. Abukawa H, Oriel BS, Leaf J et al (2013) Growth factor directed chondrogenic differentiation of porcine bone marrow-derived progenitor cells. J Craniofac Surg 24:1026–1030. doi:10.1097/SCS.0b013e31827ff323

    PubMed  Google Scholar 

  82. Bai X, Li G, Zhao C et al (2011) BMP7 induces the differentiation of bone marrow-derived mesenchymal cells into chondrocytes. Med Biol Eng Comput 49:687–692. doi:10.1007/s11517-010-0729-4

    PubMed  Google Scholar 

  83. Carlberg AL, Pucci B, Rallapalli R et al (2001) Efficient chondrogenic differentiation of mesenchymal cells in micromass culture by retroviral gene transfer of BMP-2. Differentiation 67:128–138. doi:10.1046/j.1432-0436.2001.670405.x

    CAS  PubMed  Google Scholar 

  84. Nochi H, Sung JH, Lou J et al (2004) Adenovirus mediated BMP-13 gene transfer induces chondrogenic differentiation of murine mesenchymal progenitor cells. J Bone Miner Res 19:111–122. doi:10.1359/jbmr.2004.19.1.111

    CAS  PubMed  Google Scholar 

  85. Palmer GD, Steinert A, Pascher A et al (2005) Gene-induced chondrogenesis of primary mesenchymal stem cells in vitro. Mol Ther 12:219–228. doi:10.1016/j.ymthe.2005.03.024

    CAS  PubMed  Google Scholar 

  86. Park J, Gelse K, Frank S et al (2006) Transgene-activated mesenchymal cells for articular cartilage repair: a comparison of primary bone marrow-, perichondrium/periosteum- and fat-derived cells. J Gene Med 8:112–125. doi:10.1002/jgm.826

    CAS  PubMed  Google Scholar 

  87. Steinert AF, Palmer GD, Pilapil C et al (2009) Enhanced in vitro chondrogenesis of primary mesenchymal stem cells by combined gene transfer. Tissue Eng Part A 15:1127–1139. doi:10.1089/ten.tea.2007.0252

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Wang C, Ruan D-K, Zhang C et al (2011) Effects of adeno-associated virus-2-mediated human BMP-7 gene transfection on the phenotype of nucleus pulposus cells. J Orthop Res 29:838–845. doi:10.1002/jor.21310

    CAS  PubMed  Google Scholar 

  89. Ahmed TAE, Hincke MT (2014) Mesenchymal stem cell - based tissue engineering strategies for repair of articular cartilage. Histol Histopathol 29:669–689

    CAS  PubMed  Google Scholar 

  90. Steinert AF, Proffen B, Kunz M et al (2009) Hypertrophy is induced during the in vitro chondrogenic differentiation of human mesenchymal stem cells by bone morphogenetic protein-2 and bone morphogenetic protein-4 gene transfer. Arthritis Res Ther 11:R148. doi:10.1186/ar2822

    PubMed Central  PubMed  Google Scholar 

  91. Caron MMJ, Emans PJ, Cremers A et al (2013) Hypertrophic differentiation during chondrogenic differentiation of progenitor cells is stimulated by BMP-2 but suppressed by BMP-7. Osteoarthr Cartil 21:604–613. doi:10.1016/j.joca.2013.01.009

    CAS  PubMed  Google Scholar 

  92. Madry H, Cucchiarini M (2011) Clinical potential and challenges of using genetically modified cells for articular cartilage repair. Croat Med J 52:245–261

    PubMed Central  PubMed  Google Scholar 

  93. Wakitani S, Okabe T, Horibe S et al (2011) Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med 5:146–150. doi:10.1002/term.299

    PubMed  Google Scholar 

  94. Haleem AM, Singergy AAE, Sabry D et al (2010) The clinical use of human culture-expanded autologous bone marrow mesenchymal stem cells transplanted on platelet-rich fibrin glue in the treatment of articular cartilage defects: a pilot study and preliminary results. Cartil 1:253–261. doi:10.1177/1947603510366027

    Google Scholar 

  95. Slynarski K, Deszczynski J, Karpinski J (2006) Fresh bone marrow and periosteum transplantation for cartilage defects of the knee. Transplant Proc 38:318–319. doi:10.1016/j.transproceed.2005.12.075

    CAS  PubMed  Google Scholar 

  96. De Girolamo L, Bertolini G, Cervellin M et al (2010) Treatment of chondral defects of the knee with one step matrix-assisted technique enhanced by autologous concentrated bone marrow: in vitro characterisation of mesenchymal stem cells from iliac crest and subchondral bone. Injury 41:1172–1177. doi:10.1016/j.injury.2010.09.027

    PubMed  Google Scholar 

  97. Zhang Y, Wang F, Chen J et al (2012) Bone marrow-derived mesenchymal stem cells versus bone marrow nucleated cells in the treatment of chondral defects. Int Orthop 36:1079–1086. doi:10.1007/s00264-011-1362-z

    PubMed Central  PubMed  Google Scholar 

  98. Gigante A, Calcagno S, Cecconi S et al (2011) Use of collagen scaffold and autologous bone marrow concentrate as a one-step cartilage repair in the knee: histological results of second-look biopsies at 1 year follow-up. Int J Immunopathol Pharmacol 24:69–72

    CAS  PubMed  Google Scholar 

  99. Buda R, Vannini F, Cavallo M et al (2010) Osteochondral lesions of the knee: a new one-step repair technique with bone-marrow-derived cells. J Bone Joint Surg Am 92(Suppl 2):2–11. doi:10.2106/JBJS.J.00813

    PubMed  Google Scholar 

  100. Ivkovic A, Pascher A, Hudetz D et al (2010) Articular cartilage repair by genetically modified bone marrow aspirate in sheep. Gene Ther 17:779–789. doi:10.1038/gt.2010.16

    CAS  PubMed  Google Scholar 

  101. De Windt TS, Hendriks JAA, Zhao X et al (2014) Concise review: unraveling stem cell cocultures in regenerative medicine: which cell interactions steer cartilage regeneration and how? Stem Cells Transl Med 3(6):723–733. doi:10.5966/sctm.2013-0207

    Google Scholar 

  102. Bian L, Zhai DY, Mauck RL, Burdick JA (2011) Coculture of human mesenchymal stem cells and articular chondrocytes reduces hypertrophy and enhances functional properties of engineered cartilage. Tissue Eng Part A 17:1137–1145. doi:10.1089/ten.TEA.2010.0531

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Liu X, Sun H, Yan D et al (2010) In vivo ectopic chondrogenesis of BMSCs directed by mature chondrocytes. Biomaterials 31:9406–9414. doi:10.1016/j.biomaterials.2010.08.052

    CAS  PubMed  Google Scholar 

  104. Bekkers JEJ, Tsuchida AI, van Rijen MHP et al (2013) Single-stage cell-based cartilage regeneration using a combination of chondrons and mesenchymal stromal cells: comparison with microfracture. Am J Sports Med 41:2158–2166. doi:10.1177/0363546513494181

    PubMed  Google Scholar 

  105. Spadaccio C, Rainer A, Trombetta M et al (2009) Poly-L-lactic acid/hydroxyapatite electrospun nanocomposites induce chondrogenic differentiation of human MSC. Ann Biomed Eng 37:1376–1389. doi:10.1007/s10439-009-9704-3

    PubMed  Google Scholar 

  106. Kon E, Delcogliano M, Filardo G et al (2011) Novel nano-composite multilayered biomaterial for osteochondral regeneration: a pilot clinical trial. Am J Sports Med 39:1180–1190. doi:10.1177/0363546510392711

    PubMed  Google Scholar 

  107. Hu J, Feng K, Liu X, Ma PX (2009) Chondrogenic and osteogenic differentiations of human bone marrow-derived mesenchymal stem cells on a nanofibrous scaffold with designed pore network. Biomaterials 30:5061–5067. doi:10.1016/j.biomaterials.2009.06.013

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Li W-J, Chiang H, Kuo T-F et al (2009) Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study. J Tissue Eng Regen Med 3:1–10. doi:10.1002/term.127

    CAS  PubMed Central  PubMed  Google Scholar 

  109. He L, Liu B, **peng G et al (2009) Microstructure and properties of nano-fibrous PCL-b-PLLA scaffolds for cartilage tissue engineering. Eur Cell Mater 18:63–74

    CAS  PubMed  Google Scholar 

  110. Zheng X, Yang F, Wang S et al (2011) Fabrication and cell affinity of biomimetic structured PLGA/articular cartilage ECM composite scaffold. J Mater Sci Mater Med 22:693–704. doi:10.1007/s10856-011-4248-0

    CAS  PubMed  Google Scholar 

  111. Spoliti M, Iudicone P, Leone R et al (2012) In vitro release and expansion of mesenchymal stem cells by a hyaluronic acid scaffold used in combination with bone marrow. Muscles Ligaments Tendons J 2:289–294

    PubMed Central  PubMed  Google Scholar 

  112. Feng Q, Zhu M, Wei K, Bian L (2014) Cell-Mediated Degradation Regulates Human Mesenchymal Stem Cell Chondrogenesis and Hypertrophy in MMP-Sensitive Hyaluronic Acid Hydrogels. PLoS ONE 9:e99587. doi:10.1371/journal.pone.0099587

    PubMed Central  PubMed  Google Scholar 

  113. Yeh H-Y, Lin T-Y, Lin C-H et al (2013) Neocartilage formation from mesenchymal stem cells grown in type II collagen-hyaluronan composite scaffolds. Differentiation 86:171–183. doi:10.1016/j.diff.2013.11.001

    CAS  PubMed  Google Scholar 

  114. Jung M, Kaszap B, Redöhl A et al (2009) Enhanced early tissue regeneration after matrix-assisted autologous mesenchymal stem cell transplantation in full thickness chondral defects in a minipig model. Cell Transplant 18:923–932. doi:10.3727/096368909X471297

    PubMed  Google Scholar 

  115. Gobbi A, Karnatzikos G, Sankineani SR (2014) One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med 42:648–657. doi:10.1177/0363546513518007

    PubMed  Google Scholar 

  116. Li YY, Cheng HW, Cheung KMC et al (2014) Mesenchymal stem cell-collagen microspheres for articular cartilage repair: cell density and differentiation status. Acta Biomater 10:1919–1929. doi:10.1016/j.actbio.2014.01.002

    CAS  PubMed  Google Scholar 

  117. Volpi P, Bait C, Quaglia A et al (2014) Autologous collagen-induced chondrogenesis technique (ACIC) for the treatment of chondral lesions of the talus. Knee Surg Sports Traumatol Arthrosc 22:1320–1326. doi:10.1007/s00167-013-2830-3

    CAS  PubMed  Google Scholar 

  118. Alves da Silva ML, Martins A, Costa-Pinto AR et al (2011) Chondrogenic differentiation of human bone marrow mesenchymal stem cells in chitosan-based scaffolds using a flow-perfusion bioreactor. J Tissue Eng Regen Med 5:722–732. doi:10.1002/term.372

    CAS  PubMed  Google Scholar 

  119. Ragetly GR, Griffon DJ, Lee H-B et al (2010) Effect of chitosan scaffold microstructure on mesenchymal stem cell chondrogenesis. Acta Biomater 6:1430–1436. doi:10.1016/j.actbio.2009.10.040

    CAS  PubMed  Google Scholar 

  120. Oliveira JT, Gardel LS, Rada T et al (2010) Injectable gellan gum hydrogels with autologous cells for the treatment of rabbit articular cartilage defects. J Orthop Res 28:1193–1199. doi:10.1002/jor.21114

    CAS  PubMed  Google Scholar 

  121. Park H, Temenoff JS, Tabata Y et al (2009) Effect of dual growth factor delivery on chondrogenic differentiation of rabbit marrow mesenchymal stem cells encapsulated in injectable hydrogel composites. J Biomed Mater Res A 88:889–897. doi:10.1002/jbm.a.31948

    PubMed  Google Scholar 

  122. Murdoch AD, Grady LM, Ablett MP et al (2007) Chondrogenic differentiation of human bone marrow stem cells in transwell cultures: generation of scaffold-free cartilage. Stem Cells 25:2786–2796. doi:10.1634/stemcells.2007-0374

    CAS  PubMed  Google Scholar 

  123. Maeda S, Fujitomo T, Okabe T et al (2011) Shrinkage-free preparation of scaffold-free cartilage-like disk-shaped cell sheet using human bone marrow mesenchymal stem cells. J Biosci Bioeng 111:489–492. doi:10.1016/j.jbiosc.2010.11.022

    CAS  PubMed  Google Scholar 

  124. Tian H, Zhang B, Tian Q et al (2013) Construction of self-assembled cartilage tissue from bone marrow mesenchymal stem cells induced by hypoxia combined with GDF-5. J Huazhong Univ Sci Technol Med Sci 33:700–706. doi:10.1007/s11596-013-1183-y

    CAS  PubMed  Google Scholar 

  125. Sato Y, Wakitani S, Takagi M (2013) Xeno-free and shrinkage-free preparation of scaffold-free cartilage-like disc-shaped cell sheet using human bone marrow mesenchymal stem cells. J Biosci Bioeng 116:734–739. doi:10.1016/j.jbiosc.2013.05.019

    CAS  PubMed  Google Scholar 

  126. Murphy JM, Fink DJ, Hunziker EB, Barry FP (2003) Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 48:3464–3474. doi:10.1002/art.11365

    PubMed  Google Scholar 

  127. Mokbel AN, El Tookhy OS, Shamaa AA et al (2011) Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model. BMC Musculoskelet Disord 12:259. doi:10.1186/1471-2474-12-259

    CAS  PubMed Central  PubMed  Google Scholar 

  128. Toghraie FS, Chenari N, Gholipour MA et al (2011) Treatment of osteoarthritis with infrapatellar fat pad derived mesenchymal stem cells in Rabbit. Knee 18:71–75. doi:10.1016/j.knee.2010.03.001

    CAS  PubMed  Google Scholar 

  129. Sato M, Uchida K, Nakajima H et al (2012) Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther 14:R31. doi:10.1186/ar3735

    CAS  PubMed Central  PubMed  Google Scholar 

  130. Al Faqeh H, Nor Hamdan BMY, Chen HC et al (2012) The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model. Exp Gerontol 47:458–464. doi:10.1016/j.exger.2012.03.018

    PubMed  Google Scholar 

  131. Jiang L, Ma A, Song L et al (2013) Cartilage regeneration by selected chondrogenic clonal mesenchymal stem cells in the collagenase-induced monkey osteoarthritis model. J Tissue Eng Regen Med. doi:10.1002/term.1676

    Google Scholar 

  132. Matsumoto T, Cooper GM, Gharaibeh B et al (2009) Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1. Arthritis Rheum 60:1390–1405. doi:10.1002/art.24443

    PubMed  Google Scholar 

  133. Wong KL, Lee KBL, Tai BC et al (2013) Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years’ follow-up. Arthroscopy 29:2020–2028. doi:10.1016/j.arthro.2013.09.074

    PubMed  Google Scholar 

  134. Lee KBL, Wang VTZ, Chan YH, Hui JHP (2012) A novel, minimally-invasive technique of cartilage repair in the human knee using arthroscopic microfracture and injections of mesenchymal stem cells and hyaluronic acid–a prospective comparative study on safety and short-term efficacy. Ann Acad Med Singap 41:511–517

    PubMed  Google Scholar 

  135. Kim YS, Park EH, Kim YC, Koh YG (2013) Clinical outcomes of mesenchymal stem cell injection with arthroscopic treatment in older patients with osteochondral lesions of the talus. Am J Sports Med 41:1090–1099. doi:10.1177/0363546513479018

    PubMed  Google Scholar 

  136. Centeno CJ, Busse D, Kisiday J et al (2008) Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician 11:343–353

    PubMed  Google Scholar 

  137. Emadedin M, Aghdami N, Taghiyar L et al. (2012) Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med 15:422–428. doi: 012157/AIM.0010

  138. Orozco L, Munar A, Soler R et al (2013) Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation 95:1535–1541. doi:10.1097/TP.0b013e318291a2da

    CAS  PubMed  Google Scholar 

  139. Peeters CMM, Leijs MJC, Reijman M et al (2013) Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: a systematic literature review. Osteoarthr Cartil 21:1465–1473. doi:10.1016/j.joca.2013.06.025

    CAS  PubMed  Google Scholar 

  140. Koga H, Shimaya M, Muneta T et al (2008) Local adherent technique for transplanting mesenchymal stem cells as a potential treatment of cartilage defect. Arthritis Res Ther 10:R84. doi:10.1186/ar2460

    PubMed Central  PubMed  Google Scholar 

  141. Kamei G, Kobayashi T, Ohkawa S et al (2013) Articular cartilage repair with magnetic mesenchymal stem cells. Am J Sports Med 41:1255–1264. doi:10.1177/0363546513483270

    PubMed  Google Scholar 

  142. Kobayashi T, Ochi M, Yanada S et al (2008) A novel cell delivery system using magnetically labeled mesenchymal stem cells and an external magnetic device for clinical cartilage repair. Arthroscopy 24:69–76. doi:10.1016/j.arthro.2007.08.017

    PubMed  Google Scholar 

  143. Fu W-L, Zhou C-Y, Yu J-K (2013) A new source of mesenchymal stem cells for articular cartilage repair: MSCs derived from mobilized peripheral blood share similar biological characteristics in vitro and chondrogenesis in vivo as MSCs from bone marrow in a rabbit model. Am J Sports Med. doi:10.1177/0363546513512778

    Google Scholar 

  144. Marmotti A, Bonasia DE, Bruzzone M et al (2013) Human cartilage fragments in a composite scaffold for single-stage cartilage repair: an in vitro study of the chondrocyte migration and the influence of TGF-β1 and G-CSF. Knee Surg Sports Traumatol Arthrosc 21:1819–1833. doi:10.1007/s00167-012-2244-7

    CAS  PubMed  Google Scholar 

  145. Deng M-W, Wei S-J, Yew T-L et al (2014) Cell therapy with G-CSF-mobilized stem cells in a rat osteoarthritis model. Cell Transplant. doi:10.3727/096368914X680091

    PubMed Central  Google Scholar 

  146. Horie M, Sekiya I, Muneta T et al (2009) Intra-articular Injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization to distant organs in rat massive meniscal defect. Stem Cells 27:878–887. doi:10.1634/stemcells.2008-0616

    CAS  PubMed  Google Scholar 

  147. Moriguchi Y, Tateishi K, Ando W et al (2013) Repair of meniscal lesions using a scaffold-free tissue-engineered construct derived from allogenic synovial MSCs in a miniature swine model. Biomaterials 34:2185–2193. doi:10.1016/j.biomaterials.2012.11.039

    CAS  PubMed  Google Scholar 

  148. Horie M, Choi H, Lee RH et al (2012) Intra-articular injection of human mesenchymal stem cells (MSCs) promote rat meniscal regeneration by being activated to express Indian hedgehog that enhances expression of type II collagen. Osteoarthr Cartil 20:1197–1207. doi:10.1016/j.joca.2012.06.002

    CAS  PubMed Central  PubMed  Google Scholar 

  149. Hatsushika D, Muneta T, Horie M et al (2013) Intraarticular injection of synovial stem cells promotes meniscal regeneration in a rabbit massive meniscal defect model. J Orthop Res 31:1354–1359. doi:10.1002/jor.22370

    CAS  PubMed  Google Scholar 

  150. Horie M, Driscoll MD, Sampson HW et al (2012) Implantation of allogenic synovial stem cells promotes meniscal regeneration in a rabbit meniscal defect model. J Bone Joint Surg Am 94:701–712. doi:10.2106/JBJS.K.00176

    PubMed Central  PubMed  Google Scholar 

  151. Kim SS, Kang MS, Lee KY et al (2012) Therapeutic effects of mesenchymal stem cells and hyaluronic Acid injection on osteochondral defects in rabbits’ knees. Knee Surg Relat Res 24:164–172. doi:10.5792/ksrr.2012.24.3.164

    PubMed Central  PubMed  Google Scholar 

  152. Hatsushika D, Muneta T, Nakamura T et al (2014) Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model. Osteoarthr Cartil. doi:10.1016/j.joca.2014.04.028

    PubMed  Google Scholar 

  153. Vangsness CT Jr, Farr J 2nd, Boyd J et al (2014) Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am 96:90–98. doi:10.2106/JBJS.M.00058

    PubMed  Google Scholar 

  154. Katagiri H, Muneta T, Tsuji K et al (2013) Transplantation of aggregates of synovial mesenchymal stem cells regenerates meniscus more effectively in a rat massive meniscal defect. Biochem Biophys Res Commun 435:603–609. doi:10.1016/j.bbrc.2013.05.026

    CAS  PubMed  Google Scholar 

  155. Yamasaki T, Deie M, Shinomiya R et al (2005) Meniscal regeneration using tissue engineering with a scaffold derived from a rat meniscus and mesenchymal stromal cells derived from rat bone marrow. J Biomed Mater Res A 75:23–30. doi:10.1002/jbm.a.30369

    PubMed  Google Scholar 

  156. Yamasaki T, Deie M, Shinomiya R et al (2008) Transplantation of meniscus regenerated by tissue engineering with a scaffold derived from a rat meniscus and mesenchymal stromal cells derived from rat bone marrow. Artif Organs 32:519–524. doi:10.1111/j.1525-1594.2008.00580.x

    CAS  PubMed  Google Scholar 

  157. Scotti C, Hirschmann MT, Antinolfi P et al (2013) Meniscus repair and regeneration: review on current methods and research potential. Eur Cell Mater 26:150–170

    CAS  PubMed  Google Scholar 

  158. Walsh CJ, Goodman D, Caplan AI, Goldberg VM (1999) Meniscus regeneration in a rabbit partial meniscectomy model. Tissue Eng 5:327–337

    CAS  PubMed  Google Scholar 

  159. Izuta Y, Ochi M, Adachi N et al (2005) Meniscal repair using bone marrow-derived mesenchymal stem cells: experimental study using green fluorescent protein transgenic rats. Knee 12:217–223. doi:10.1016/j.knee.2001.06.001

    PubMed  Google Scholar 

  160. Angele P, Johnstone B, Kujat R et al (2008) Stem cell based tissue engineering for meniscus repair. J Biomed Mater Res A 85:445–455. doi:10.1002/jbm.a.31480

    PubMed  Google Scholar 

  161. Mandal BB, Park S-H, Gil ES, Kaplan DL (2011) Stem cell-based meniscus tissue engineering. Tissue Eng Part A 17:2749–2761. doi:10.1089/ten.TEA.2011.0031

    CAS  PubMed Central  PubMed  Google Scholar 

  162. Pabbruwe MB, Kafienah W, Tarlton JF et al (2010) Repair of meniscal cartilage white zone tears using a stem cell/collagen-scaffold implant. Biomaterials 31:2583–2591. doi:10.1016/j.biomaterials.2009.12.023

    CAS  PubMed  Google Scholar 

  163. Zellner J, Hierl K, Mueller M et al (2013) Stem cell-based tissue-engineering for treatment of meniscal tears in the avascular zone. J Biomed Mater Res Part B Appl Biomater 101:1133–1142. doi:10.1002/jbm.b.32922

    PubMed  Google Scholar 

  164. Baker BM, Mauck RL (2007) The effect of nanofiber alignment on the maturation of engineered meniscus constructs. Biomaterials 28:1967–1977. doi:10.1016/j.biomaterials.2007.01.004

    CAS  PubMed Central  PubMed  Google Scholar 

  165. Yamanaka S (2007) Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell 1:39–49. doi:10.1016/j.stem.2007.05.012

    CAS  PubMed  Google Scholar 

  166. Takahashi K, Tanabe K, Ohnuki M et al (2014) Induction of pluripotency in human somatic cells via a transient state resembling primitive streak-like mesendoderm. Nat Commun 5:3678. doi:10.1038/ncomms4678

    PubMed  Google Scholar 

  167. Ko J-Y, Kim K-I, Park S, Im G-I (2014) In vitro chondrogenesis and in vivo repair of osteochondral defect with human induced pluripotent stem cells. Biomaterials 35:3571–3581. doi:10.1016/j.biomaterials.2014.01.009

    CAS  PubMed  Google Scholar 

  168. Marmotti A (2014) A future in our past: the umbilical cord for orthopaedic tissue engineering. Joints 2(1):20-25

  169. Ishige I, Nagamura-Inoue T, Honda MJ et al (2009) Comparison of mesenchymal stem cells derived from arterial, venous, and Wharton’s jelly explants of human umbilical cord. Int J Hematol 90:261–269. doi:10.1007/s12185-009-0377-3

    PubMed  Google Scholar 

  170. Jäger M, Zilkens C, Bittersohl B, Krauspe R (2009) Cord blood–an alternative source for bone regeneration. Stem Cell Rev 5:266–277. doi:10.1007/s12015-009-9083-z

    PubMed  Google Scholar 

  171. Berg L, Koch T, Heerkens T et al (2009) Chondrogenic potential of mesenchymal stromal cells derived from equine bone marrow and umbilical cord blood. Vet Comp Orthop Traumatol 22:363–370. doi:10.3415/VCOT-08-10-0107

    CAS  PubMed  Google Scholar 

  172. Arufe MC, De la Fuente A, Mateos J et al (2011) Analysis of the chondrogenic potential and secretome of mesenchymal stem cells derived from human umbilical cord stroma. Stem Cells Dev 20:1199–1212. doi:10.1089/scd.2010.0315

    CAS  PubMed  Google Scholar 

  173. Marmotti A, Mattia S, Bruzzone M et al (2012) Minced umbilical cord fragments as a source of cells for orthopaedic tissue engineering: an in vitro study. Stem Cells Int 2012:326813. doi:10.1155/2012/326813

    CAS  PubMed Central  PubMed  Google Scholar 

  174. Liu S, Yuan M, Hou K et al (2012) Immune characterization of mesenchymal stem cells in human umbilical cord Wharton’s jelly and derived cartilage cells. Cell Immunol 278:35–44. doi:10.1016/j.cellimm.2012.06.010

    CAS  PubMed  Google Scholar 

  175. Ichim TE, Solano F, Lara F et al (2010) Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report. Int Arch Med 3:30. doi:10.1186/1755-7682-3-30

    PubMed Central  PubMed  Google Scholar 

  176. Guilak F, Estes BT, Diekman BO et al (2010) 2010 Nicolas Andry award: multipotent adult stem cells from adipose tissue for musculoskeletal tissue engineering. Clin Orthop Relat Res 468:2530–2540. doi:10.1007/s11999-010-1410-9

    PubMed Central  PubMed  Google Scholar 

  177. James AW, Zara JN, Corselli M et al (2012) An abundant perivascular source of stem cells for bone tissue engineering. Stem Cells Transl Med 1:673–684. doi:10.5966/sctm.2012-0053

    CAS  PubMed Central  PubMed  Google Scholar 

  178. Gimble JM, Guilak F, Bunnell BA (2010) Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells. Stem Cell Res Ther 1:19. doi:10.1186/scrt19

    PubMed Central  PubMed  Google Scholar 

  179. Koh Y-G, Choi Y-J, Kwon S-K et al (2013) Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. doi:10.1007/s00167-013-2807-2

    Google Scholar 

  180. Behfar M, Javanmardi S, Eghbal Khajehrahimi A, Sarrafzadeh-Rezaei F (2013) Comparative study on functional efects of alotransplantation of bone marrow stromal cells and adipose derived stromal vascular fraction on tendon repair: a biomechanical study in rabbits. Cell J 16:6

  181. Jurgens WJFM, Kroeze RJ, Zandieh-Doulabi B et al (2013) One-step surgical procedure for the treatment of osteochondral defects with adipose-derived stem cells in a caprine knee defect: a pilot study. Biores Open Access 2:315–325. doi:10.1089/biores.2013.0024

    CAS  PubMed Central  PubMed  Google Scholar 

  182. Pak J, Lee JH, Lee SH (2013) A novel biological approach to treat chondromalacia patellae. PLoS ONE 8:e64569. doi:10.1371/journal.pone.0064569

    CAS  PubMed Central  PubMed  Google Scholar 

  183. Müller AM, Mehrkens A, Schäfer DJ et al (2010) Towards an intraoperative engineering of osteogenic and vasculogenic grafts from the stromal vascular fraction of human adipose tissue. Eur Cell Mater 19:127–135

    PubMed  Google Scholar 

  184. Izadpanah R, Trygg C, Patel B et al (2006) Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 99:1285–1297. doi:10.1002/jcb.20904

    CAS  PubMed Central  PubMed  Google Scholar 

  185. Schäffler A, Büchler C (2007) Concise review: adipose tissue-derived stromal cells–basic and clinical implications for novel cell-based therapies. Stem Cells 25:818–827. doi:10.1634/stemcells.2006-0589

    PubMed  Google Scholar 

  186. Uysal AC, Mizuno H (2011) Differentiation of adipose-derived stem cells for tendon repair. Methods Mol Biol 702:443–451. doi:10.1007/978-1-61737-960-4_32

    CAS  PubMed  Google Scholar 

  187. Lopa S, Colombini A, Stanco D et al (2014) Donor-matched mesenchymal stem cells from knee infrapatellar and subcutaneous adipose tissue of osteoarthritic donors display differential chondrogenic and osteogenic commitment. Eur Cell Mater 27:298–311

    CAS  PubMed  Google Scholar 

  188. Liang H, Li X, Shimer AL et al (2014) A novel strategy of spine defect repair with a degradable bioactive scaffold preloaded with adipose-derived stromal cells. Spine J 14:445–454. doi:10.1016/j.spinee.2013.09.045

    PubMed  Google Scholar 

  189. Koh Y-G, Jo S-B, Kwon O-R et al (2013) Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy 29:748–755. doi:10.1016/j.arthro.2012.11.017

    PubMed  Google Scholar 

  190. Jo CH, Lee YG, Shin WH et al (2014) Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells 32:1254–1266. doi:10.1002/stem.1634

    CAS  PubMed  Google Scholar 

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Acknowledgments

We are grateful to Marco Forni (MD) for cytological and histological assistance, and critical observations. We would also like to thank Radhika Srinivasan, PhD, for precious editing of the manuscript.

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The authors indicate no potential conflicts of interests.

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Marmotti, A., de Girolamo, L., Bonasia, D.E. et al. Bone marrow derived stem cells in joint and bone diseases: a concise review. International Orthopaedics (SICOT) 38, 1787–1801 (2014). https://doi.org/10.1007/s00264-014-2445-4

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