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Stem Cells International
Volume 2012, Article ID 168385, 9 pages
http://dx.doi.org/10.1155/2012/168385
Review Article

Stem Cells and Gene Therapy for Cartilage Repair

1Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo 200, Trigoria, 00128 Rome, Italy
2Centro Integrato di Ricerca (CIR), Università Campus Bio-Medico, Via Alvaro del Portillo, 21, 00128, Rome, Italy
3Centre for Sports and Exercise Medicine, Barts and The London School of Medicine and Dentistry, Mile End Hospital, 275 Bancroft Road, London E1 4DG, UK

Received 15 October 2011; Accepted 6 December 2011

Academic Editor: Wasim S. Khan

Copyright © 2012 Umile Giuseppe Longo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. A. Buckwalter and H. J. Mankin, “Articular cartilage: tissue design and chondrocyte-matrix interactions,” Instructional course lectures, vol. 47, pp. 477–486, 1998. View at Google Scholar · View at Scopus
  2. E. B. Hunziker, “Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects,” Osteoarthritis and Cartilage, vol. 10, no. 6, pp. 432–463, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. J. A. Buckwalter and H. J. Mankin, “Articular cartilage repair and transplantation,” Arthritis and Rheumatism, vol. 41, no. 8, pp. 1331–1342, 1998. View at Publisher · View at Google Scholar · View at Scopus
  4. T. Minas, “The role of cartilage repair techniques, including chondrocyte transplantation, in focal chondral knee damage,” Instructional course lectures, vol. 48, pp. 629–643, 1999. View at Google Scholar · View at Scopus
  5. J. R. Steadman, W. G. Rodkey, and K. K. Briggs, “Microfracture to treat full-thickness chondral defects: surgical technique, rehabilitation, and outcomes,” The journal of knee surgery, vol. 15, no. 3, pp. 170–176, 2002. View at Google Scholar · View at Scopus
  6. S. J. M. Bouwmeester, J. M. H. Beckers, R. Kuijer, A. J. Van Der Linden, and S. K. Bulstra, “Long-term results of rib perichondrial grafts for repair of cartilage defects in the human knee,” International Orthopaedics, vol. 21, no. 5, pp. 313–317, 1997. View at Publisher · View at Google Scholar · View at Scopus
  7. A. I. Caplan, M. Elyaderani, Y. Mochizuki, S. Wakitani, and V. M. Goldberg, “Principles of cartilage repair and regeneration,” Clinical Orthopaedics and Related Research, no. 342, pp. 254–269, 1997. View at Google Scholar · View at Scopus
  8. L. Hangody and P. Füles, “Autologous osteochondral mosaicplasty for the treatment of full-thickness defects of weight-bearing joints: ten years of experimental and clinical experience,” Journal of Bone and Joint Surgery A, vol. 85, no. 1, pp. 25–32, 2003. View at Google Scholar · View at Scopus
  9. M. Brittberg, A. Lindahl, A. Nilsson, C. Ohlsson, O. Isaksson, and L. Peterson, “Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation,” New England Journal of Medicine, vol. 331, no. 14, pp. 889–895, 1994. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. T. Minas and S. Nehrer, “Current concepts in the treatment of articular cartilage defects,” Orthopedics, vol. 20, no. 6, pp. 525–538, 1997. View at Google Scholar · View at Scopus
  11. L. Peterson, T. Minas, M. Brittberg, and A. Lindahl, “Treatment of osteochondritis dissecans of the knee with autologous chondrocyte transplantation: results at two to ten years,” Journal of Bone and Joint Surgery A, vol. 85, no. 1, pp. 17–24, 2003. View at Google Scholar · View at Scopus
  12. P. Behrens, U. Bosch, J. Bruns et al., “Recommendations for indication and application of ACT of the joined advisory board of the German Societies for Traumatology (DGU) and Orthopaedic Surgery (DGOOC),” Zeitschrift fur Orthopadie und Ihre Grenzgebiete, vol. 142, no. 5, pp. 529–539, 2004. View at Publisher · View at Google Scholar · View at PubMed
  13. S. Marlovits, P. Zeller, P. Singer, C. Resinger, and V. Vécsei, “Cartilage repair: generations of autologous chondrocyte transplantation,” European Journal of Radiology, vol. 57, no. 1, pp. 24–31, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. L. Peterson, M. Brittberg, I. Kiviranta, E. L. Åkerlund, and A. Lindahl, “Autologous chondrocyte transplantation: biomechanics and long-term durability,” American Journal of Sports Medicine, vol. 30, no. 1, pp. 2–12, 2002. View at Google Scholar · View at Scopus
  15. C. K. Kuo, W. J. Li, R. L. Mauck, and R. S. Tuan, “Cartilage tissue engineering: its potential and uses,” Current Opinion in Rheumatology, vol. 18, no. 1, pp. 64–73, 2006. View at Publisher · View at Google Scholar · View at MathSciNet · View at Scopus
  16. R. Tuli, W. J. Li, and R. S. Tuan, “Current state of cartilage tissue engineering,” Arthritis Research and Therapy, vol. 5, no. 5, pp. 235–238, 2003. View at Google Scholar · View at Scopus
  17. C. H. Evans, H. J. Mankin, A. B. Ferguson et al., “Clinical trial to assess the safety, feasibility, and efficacy of transferring a potentially anti-arthritic cytokine gene to human joints with rheumatoid arthritis,” Human Gene Therapy, vol. 7, no. 10, pp. 1261–1280, 1996. View at Google Scholar · View at Scopus
  18. C. H. Evans, P. D. Robbins, S. C. Ghivizzani et al., “Gene transfer to human joints: progress toward a gene therapy of arthritis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 24, pp. 8698–8703, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  19. R. M. Dharmavaram, G. Liu, R. S. Tuan, D. G. Stokes, and S. A. Jiménez, “Stable transfection of human fetal chondrocytes with a type II procollagen minigene: expression of the mutant protein and alterations in the structure of the extracellular matrix in vitro,” Arthritis and Rheumatism, vol. 42, no. 7, pp. 1433–1442, 1999. View at Publisher · View at Google Scholar · View at Scopus
  20. V. Lefebvre, R. R. Behringer, and B. De Crombrugghe, “L-Sox5, Sox6 and SOx9 control essential steps of the chondrocyte differentiation pathway,” Osteoarthritis and Cartilage, vol. 9, pp. S69–S75, 2001. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Hoffmann and G. Gross, “BMP signaling pathways in cartilage and bone formation,” Critical Reviews in Eukaryotic Gene Expression, vol. 11, no. 1–3, pp. 23–45, 2001. View at Google Scholar · View at Scopus
  22. A. Vortkamp, “Interaction of growth factors regulating chondrocyte differentiation in the developing embryo,” Osteoarthritis and Cartilage, vol. 9, pp. S109–S117, 2001. View at Google Scholar · View at Scopus
  23. P. D. Robbins, C. H. Evans, and Y. Chernajovsky, “Gene therapy for arthritis,” Gene Therapy, vol. 10, no. 10, pp. 902–911, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. D. D. D'Lima, S. Hashimoto, P. C. Chen, C. W. Colwell Jr., and M. K. Lotz, “Impact of mechanical trauma on matrix and cells,” Clinical Orthopaedics and Related Research, no. 391, pp. S90–S99, 2001. View at Google Scholar · View at Scopus
  25. D. D. D'Lima, S. Hashimoto, P. C. Chen, M. K. Lotz, and C. W. Colwell Jr., “Cartilage injury induces chondrocyte apoptosis,” Journal of Bone and Joint Surgery A, vol. 83, no. 2, pp. 19–21, 2001. View at Google Scholar · View at Scopus
  26. J. L. Haupt, D. D. Frisbie, C. W. McIlwraith et al., “Dual transduction of insulin-like growth factor-I and interleukin-1 receptor antagonist protein controls cartilage degradation in an osteoarthritic culture model,” Journal of Orthopaedic Research, vol. 23, no. 1, pp. 118–126, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  27. A. J. Nixon, J. L. Haupt, D. D. Frisbie et al., “Gene-mediated restoration of cartilage matrix by combination insulin-like growth factor-I/interleukin-1 receptor antagonist therapy,” Gene Therapy, vol. 12, no. 2, pp. 177–186, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. A. F. Steinert, U. Nöth, and R. S. Tuan, “Concepts in gene therapy for cartilage repair,” Injury, vol. 39, no. 1, pp. 97–113, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. S. C. Ghivizzani, E. R. Lechman, R. Kang et al., “Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis factor α soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 8, pp. 4613–4618, 1998. View at Publisher · View at Google Scholar · View at Scopus
  30. S. C. Ghivizzani, E. R. Lechman, C. Tio et al., “Direct retrovirus-mediated gene transfer to the synovium of the rabbit knee: implications for arthritis gene therapy,” Gene Therapy, vol. 4, no. 9, pp. 977–982, 1997. View at Google Scholar · View at Scopus
  31. S. C. Ghivizzani, T. J. Oligino, J. C. Glorioso, P. D. Robbins, and C. H. Evans, “Direct gene delivery strategies for the treatment of rheumatoid arthritis,” Drug Discovery Today, vol. 6, no. 5, pp. 259–267, 2001. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Cucchiarini, H. Madry, C. Ma et al., “Improved tissue repair in articular cartilage defects in vivo by rAAV-mediated overexpression of human fibroblast growth factor 2,” Molecular Therapy, vol. 12, no. 2, pp. 229–238, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. E. Gouze, R. Pawliuk, C. Pilapil et al., “In vivo gene delivery to synovium by lentiviral vectors,” Molecular Therapy, vol. 5, no. 4, pp. 397–404, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. T. Tomita, H. Hashimoto, N. Tomita et al., “In vivo direct gene transfer into articular cartilage by intraarticular injection mediated by HVJ (Sendai virus) and liposomes,” Arthritis and Rheumatism, vol. 40, no. 5, pp. 901–906, 1997. View at Google Scholar · View at Scopus
  35. Q. Yao, J. C. Glorioso, C. H. Evans et al., “Adenoviral mediated delivery of FAS ligand to arthritic joints causes extensive apoptosis in the synovial lining,” Journal of Gene Medicine, vol. 2, no. 3, pp. 210–219, 2000. View at Google Scholar · View at Scopus
  36. C. H. Evans, E. Gouze, J. N. Gouze, P. D. Robbins, and S. C. Ghivizzani, “Gene therapeutic approaches-transfer in vivo,” Advanced Drug Delivery Reviews, vol. 58, no. 2, pp. 243–258, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. C. H. Evans, J. N. Gouze, E. Gouze, P. D. Robbins, and S. C. Ghivizzani, “Osteoarthritis gene therapy,” Gene Therapy, vol. 11, no. 4, pp. 379–389, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. M. Cucchiarini and H. Madry, “Gene therapy for cartilage defects,” Journal of Gene Medicine, vol. 7, no. 12, pp. 1495–1509, 2005. View at Publisher · View at Google Scholar · View at PubMed
  39. K. Gelse and H. Schneider, “Ex vivo gene therapy approaches to cartilage repair,” Advanced Drug Delivery Reviews, vol. 58, no. 2, pp. 259–284, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. S. B. Trippel, S. C. Ghivizzani, and A. J. Nixon, “Gene-based approaches for the repair of articular cartilage,” Gene Therapy, vol. 11, no. 4, pp. 351–359, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. D. D. Frisbie, S. C. Ghivizzani, P. D. Robbins, C. H. Evans, and C. W. McIlwraith, “Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene,” Gene Therapy, vol. 9, no. 1, pp. 12–20, 2002. View at Publisher · View at Google Scholar · View at Scopus
  42. A. C. Bakker, L. A. B. Joosten, O. J. Arntz et al., “Prevention of murine collagen-induced arthritis in the knee and ipsilateral paw by local expression of human interleukin-1 receptor antagonist protein in the knee,” Arthritis and Rheumatism, vol. 40, no. 5, pp. 893–900, 1997. View at Google Scholar · View at Scopus
  43. K. Gelse, Q. J. Jiang, T. Aigner et al., “Fibroblast-mediated delivery of growth factor complementary DNA into mouse joints induces chondrogenesis but avoids the disadvantages of direct viral gene transfer,” Arthritis and Rheumatism, vol. 44, no. 8, pp. 1943–1953, 2001. View at Publisher · View at Google Scholar · View at Scopus
  44. K. Gelse, K. Von der Mark, T. Aigner, J. Park, and H. Schneider, “Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells,” Arthritis and Rheumatism, vol. 48, no. 2, pp. 430–441, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  45. Z. Mi, S. C. Ghivizzani, E. Lechman, J. C. Glorioso, C. H. Evans, and P. D. Robbins, “Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees,” Arthritis Res Ther, vol. 5, no. 3, pp. R132–R139, 2003. View at Google Scholar · View at Scopus
  46. J. Bonadio, “Tissue engineering via local gene delivery: update and future prospects for enhancing the technology,” Advanced Drug Delivery Reviews, vol. 44, no. 2-3, pp. 185–194, 2000. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Bonadio, E. Smiley, P. Patil, and S. Goldstein, “Localized, direct plasmid gene delivery in vivo: prolonged therapy results in reproducible tissue regeneration,” Nature Medicine, vol. 5, no. 7, pp. 753–759, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. Q. Dai, L. Manfield, Y. Wang, and G. A. C. Murrell, “Adenovirus-mediated gene transfer to healing tendon—enhanced efficiency using a gelatin sponge,” Journal of Orthopaedic Research, vol. 21, no. 4, pp. 604–609, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. C. H. Evans, “Gene therapies for osteoarthritis,” Current rheumatology reports, vol. 6, no. 1, pp. 31–40, 2004. View at Google Scholar · View at Scopus
  50. A. Pascher, G. D. Palmer, A. Steinert et al., “Gene delivery to cartilage defects using coagulated bone marrow aspirate,” Gene Therapy, vol. 11, no. 2, pp. 133–141, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. A. Pascher, A. F. Steinert, G. D. Palmer et al., “Enhanced repair of the anterior cruciate ligament by in situ gene transfer: evaluation in an in vitro model,” Molecular Therapy, vol. 10, no. 2, pp. 327–336, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. R. E. Samuel, C. R. Lee, S. C. Ghivizzani et al., “Delivery of plasmid DNA to articular chondrocytes via novel collagen-glycosaminoglycan matrices,” Human Gene Therapy, vol. 13, no. 7, pp. 791–802, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. H. Madry and S. B. Trippel, “Efficient lipid-mediated gene transfer to articular chondrocytes,” Gene Therapy, vol. 7, no. 4, pp. 286–291, 2000. View at Google Scholar · View at Scopus
  54. C. Hidaka, L. R. Goodrich, C. T. Chen, R. F. Warren, R. G. Crystal, and A. J. Nixon, “Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7,” Journal of Orthopaedic Research, vol. 21, no. 4, pp. 573–583, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. A. J. Nixon, L. A. Fortier, J. Williams, and H. Mohammed, “Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites,” Journal of Orthopaedic Research, vol. 17, no. 4, pp. 475–487, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. A. J. Nixon, R. A. Saxer, and B. D. Brower-Toland, “Exogenous insulin-like growth factor-I stimulates an autoinductive IGF-I autocrine/paracrine response in chondrocytes,” Journal of Orthopaedic Research, vol. 19, no. 1, pp. 26–32, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. F. D. Shuler, H. I. Georgescu, C. Niyibizi et al., “Increased matrix synthesis following adenoviral transfer of a transforming growth factor β1 gene into articular chondrocytes,” Journal of Orthopaedic Research, vol. 18, no. 4, pp. 585–592, 2000. View at Google Scholar
  58. P. Smith, F. D. Shuler, H. I. Georgescu et al., “Genetic enhancement of matrix synthesis by articular chondrocytes: comparison of different growth factor genes in the presence and absence of interleukin-1,” Arthritis and Rheumatism, vol. 43, no. 5, pp. 1156–1164, 2000. View at Publisher · View at Google Scholar · View at Scopus
  59. L. Ying, S. R. Tew, A. M. Russell, K. R. Gonzalez, T. E. Hardingham, and R. E. Hawkins, “Transduction of passaged human articular chondrocytes with adenoviral, retroviral, and lentiviral vectors and the effects of enhanced expression of SOX9,” Tissue Engineering, vol. 10, no. 3-4, pp. 575–584, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. S. R. Tew, Y. Li, P. Pothancharoen, L. M. Tweats, R. E. Hawkins, and T. E. Hardingham, “Retroviral transduction with SOX9 enhances re-expression of the chondrocyte phenotype in passaged osteoarthritic human articular chondrocytes,” Osteoarthritis and Cartilage, vol. 13, no. 1, pp. 80–89, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. H. Enomoto, M. Enomoto-Iwamoto, M. Iwamoto et al., “Cbfa1 is a positive regulatory factor in chondrocyte maturation,” Journal of Biological Chemistry, vol. 275, no. 12, pp. 8695–8702, 2000. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Iwamoto, J. Kitagaki, Y. Tamamura et al., “Runx2 expression and action in chondrocytes are regulated by retinoid signaling and parathyroid hormone-related peptide (PTHrP),” Osteoarthritis and Cartilage, vol. 11, no. 1, pp. 6–15, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. P. J. Doherty, H. Zhang, L. Tremblay, V. Manolopoulos, and K. W. Marshall, “Resurfacing of articular cartilage explants with genetically-modified human chondrocytes in vitro,” Osteoarthritis and Cartilage, vol. 6, no. 3, pp. 153–160, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. H. Madry, D. Zurakowski, and S. B. Trippel, “Overexpression of human insulin-like growth factor-I promotes new tissue formation in an ex vivo model of articular chondrocyte transplantation,” Gene Therapy, vol. 8, no. 19, pp. 1443–1449, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  65. H. Madry, G. Emkey, D. Zurakowski, and S. B. Trippel, “Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation,” Journal of Gene Medicine, vol. 6, no. 2, pp. 238–245, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. M. Cucchiarini, T. Thurn, A. Weimer, D. Kohn, E. F. Terwilliger, and H. Madry, “Restoration of the extracellular matrix in human osteoarthritic articular cartilage by overexpression of the transcription factor SOX9,” Arthritis and Rheumatism, vol. 56, no. 1, pp. 158–167, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  67. V. M. Baragi, R. R. Renkiewicz, H. Jordan, J. Bonadio, J. W. Hartman, and B. J. Roessler, “Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation,” Journal of Clinical Investigation, vol. 96, no. 5, pp. 2454–2460, 1995. View at Google Scholar · View at Scopus
  68. V. M. Baragi, R. R. Renkiewicz, L. Qiu et al., “Transplantation of adenovirally transduced allogeneic chondrocytes into articular cartilage defects in vivo,” Osteoarthritis and Cartilage, vol. 5, no. 4, pp. 275–282, 1997. View at Publisher · View at Google Scholar · View at Scopus
  69. T. Ikeda, T. Kubo, Y. Arai et al., “Adenovirus mediated gene delivery to the joints of guinea pigs,” Journal of Rheumatology, vol. 25, no. 9, pp. 1666–1673, 1998. View at Google Scholar · View at Scopus
  70. R. Kang, T. Marui, S. C. Ghivizzani et al., “Ex vivo gene transfer to chondrocytes in full-thickness articular cartilage defects: a feasibility study,” Osteoarthritis and Cartilage, vol. 5, no. 2, pp. 139–143, 1997. View at Publisher · View at Google Scholar · View at Scopus
  71. H. Madry, M. Cucchiarini, U. Stein et al., “Sustained transgene expression in cartilage defects in vivo after transplantation of articular chondrocytes modified by lipid-mediated gene transfer in a gel suspension delivery system,” Journal of Gene Medicine, vol. 5, no. 6, pp. 502–509, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  72. S. M. Richardson, J. M. Curran, R. Chen et al., “The differentiation of bone marrow mesenchymal stem cells into chondrocyte-like cells on poly-l-lactic acid (PLLA) scaffolds,” Biomaterials, vol. 27, no. 22, pp. 4069–4078, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  73. S. M. Richardson, R. V. Walker, S. Parker et al., “Intervertebral disc cell-mediated mesenchymal stem cell differentiation,” Stem Cells, vol. 24, no. 3, pp. 707–716, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  74. M. F. Pittenger, A. M. Mackay, S. C. Beck et al., “Multilineage potential of adult human mesenchymal stem cells,” Science, vol. 284, no. 5411, pp. 143–147, 1999. View at Publisher · View at Google Scholar · View at Scopus
  75. T. L. Arinzeh, “Mesenchymal stem cells for bone repair: preclinical studies and potential orthopedic applications,” Foot and Ankle Clinics, vol. 10, no. 4, pp. 651–665, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  76. L. Hong, A. Colpan, and I. A. Peptan, “Modulations of 17-β estradiol on osteogenic and adipogenic differentiations of human mesenchymal stem cells,” Tissue Engineering, vol. 12, no. 10, pp. 2747–2753, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  77. D. Noël, F. Djouad, and C. Jorgensen, “Regenerative medicine through mesenchymal stem cells for bone and cartilage repair,” Current Opinion in Investigational Drugs, vol. 3, no. 7, pp. 1000–1004, 2002. View at Google Scholar · View at Scopus
  78. F. P. Barry and J. M. Murphy, “Mesenchymal stem cells: clinical applications and biological characterization,” International Journal of Biochemistry and Cell Biology, vol. 36, no. 4, pp. 568–584, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. A. I. Caplan, “Adult mesenchymal stem cells for tissue engineering versus regenerative medicine,” Journal of Cellular Physiology, vol. 213, no. 2, pp. 341–347, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  80. W. Sonoyama, Y. Liu, D. Fang et al., “Mesenchymal stem cell-mediated functional tooth regeneration in Swine,” PLoS One, vol. 1, no. 1, article no. e79, 2006. View at Publisher · View at Google Scholar · View at PubMed
  81. O. Trubiani, R. Di Primio, T. Traini et al., “Morphological and cytofluorimetric analysis of adult mesenchymal stem cells expanded ex vivo from periodontal ligament,” International Journal of Immunopathology and Pharmacology, vol. 18, no. 2, pp. 213–221, 2005. View at Google Scholar
  82. O. Trubiani, G. Orsini, S. Caputi, and A. Piattelli, “Adult mesenchymal stem cells in dental research: a new approach for tissue engineering,” International Journal of Immunopathology and Pharmacology, vol. 19, no. 3, pp. 451–460, 2006. View at Google Scholar
  83. M. N. Helder, M. Knippenberg, J. Klein-Nulend, and P. I. J. M. Wuisman, “Stem cells from adipose tissue allow challenging new concepts for regenerative medicine,” Tissue Engineering, vol. 13, no. 8, pp. 1799–1808, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  84. S. M. Richardson, A. Mobasheri, A. J. Freemont, and J. A. Hoyland, “Intervertebral disc biology, degeneration and novel tissue engineering and regenerative medicine therapies,” Histology and histopathology, vol. 22, no. 9, pp. 1033–1041, 2007. View at Google Scholar
  85. A. E. Grigoriadis, J. N. M. Heersche, and J. E. Aubin, “Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone,” Journal of Cell Biology, vol. 106, no. 6, pp. 2139–2151, 1988. View at Google Scholar · View at Scopus
  86. C. Csaki, N. Keshishzadeh, K. Fischer, and M. Shakibaei, “Regulation of inflammation signalling by resveratrol in human chondrocytes in vitro,” Biochemical Pharmacology, vol. 75, no. 3, pp. 677–687, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  87. C. Csaki, U. Matis, A. Mobasheri, and M. Shakibaei, “Co-culture of canine mesenchymal stem cells with primary bone-derived osteoblasts promotes osteogenic differentiation,” Histochemistry and Cell Biology, vol. 131, no. 2, pp. 251–266, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  88. A. Mobasheri, C. Csaki, A. L. Clutterbuck, M. Rahmanzadeh, and M. Shakibaei, “Mesenchymal stem cells in connective tissue engineering and regenerative medicine: applications in cartilage repair and osteoarthritis therapy,” Histology and Histopathology, vol. 24, no. 3, pp. 347–366, 2009. View at Google Scholar
  89. T. Fukumoto, J. W. Sperling, A. Sanyal et al., “Combined effects of insulin-like growth factor-1 and transforming growth factor-β1 on periosteal mesenchymal cells during chondrogenesis in vitro,” Osteoarthritis and Cartilage, vol. 11, no. 1, pp. 55–64, 2003. View at Publisher · View at Google Scholar · View at Scopus
  90. H.-L. Ma, S.-C. Hung, S.-Y. Lin, Y.-L. Chen, and W.-H. Lo, “Chondrogenesis of human mesenchymal stem cells encapsulated in alginate beads,” Journal of Biomedical Materials Research A, vol. 64, no. 2, pp. 273–281, 2003. View at Google Scholar
  91. B. Johnstone, T. M. Hering, A. I. Caplan, V. M. Goldberg, and J. U. Yoo, “In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells,” Experimental Cell Research, vol. 238, no. 1, pp. 265–272, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  92. H. Jian, X. Shen, I. Liu, M. Semenov, X. He, and X. F. Wang, “Smad3-dependent nuclear translocation of β-catenin is required for TGF-β1- induced proliferation of bone marrow-derived adult human mesenchymal stem cells,” Genes and Development, vol. 20, no. 6, pp. 666–674, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  93. S. Zhou, K. Eid, and J. Glowacki, “Cooperation between TGF-β and Wnt pathways during chondrocyte and adipocyte differentiation of human marrow stromal cells,” Journal of Bone and Mineral Research, vol. 19, no. 3, pp. 463–470, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  94. M. Chiou, Y. Xu, and M. T. Longaker, “Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells,” Biochemical and Biophysical Research Communications, vol. 343, no. 2, pp. 644–652, 2006. View at Publisher · View at Google Scholar · View at PubMed
  95. M. Knippenberg, M. N. Helder, B. Zandieh Doulabi, P. I. J. M. Wuisman, and J. Klein-Nulend, “Osteogenesis versus chondrogenesis by BMP-2 and BMP-7 in adipose stem cells,” Biochemical and Biophysical Research Communications, vol. 342, no. 3, pp. 902–908, 2006. View at Publisher · View at Google Scholar · View at PubMed
  96. L. Longobardi, L. O'Rear, S. Aakula et al., “Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-β signaling,” Journal of Bone and Mineral Research, vol. 21, no. 4, pp. 626–636, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  97. L. A. Solchaga, K. Penick, J. D. Porter, V. M. Goldberg, A. I. Caplan, and J. F. Welter, “FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells,” Journal of Cellular Physiology, vol. 203, no. 2, pp. 398–409, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  98. S. Murakami, M. Kan, W. L. McKeehan, and B. De Crombrugghe, “Up-regulation of the chondrogenic Sox9 gene by fibroblast growth factors is mediated by the mitogen-activated protein kinase pathway,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 3, pp. 1113–1118, 2000. View at Publisher · View at Google Scholar · View at Scopus
  99. S. R. Tew, P. Pothacharoen, T. Katopodi, and T. E. Hardingham, “SOX9 transduction increases chondroitin sulfate synthesis in cultured human articular chondrocytes without altering glycosyltransferase and sulfotransferase transcription,” Biochemical Journal, vol. 414, no. 2, pp. 231–236, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  100. H. Tsuchiya, H. Kitoh, F. Sugiura, and N. Ishiguro, “Chondrogenesis enhanced by overexpression of sox9 gene in mouse bone marrow-derived mesenchymal stem cells,” Biochemical and Biophysical Research Communications, vol. 301, no. 2, pp. 338–343, 2003. View at Publisher · View at Google Scholar
  101. J. I. Sive, P. Baird, M. Jeziorsk, A. Watkins, J. A. Hoyland, and A. J. Freemont, “Expression of chondrocyte markers by cells of normal and degenerate intervertebral discs,” Molecular Pathology, vol. 55, no. 2, pp. 91–97, 2002. View at Publisher · View at Google Scholar · View at Scopus
  102. J. U. Yoo, T. S. Barthel, K. Nishimura et al., “The chondrogenic potential of human bone-marrow-derived mesenchymal progenitor cells,” Journal of Bone and Joint Surgery A, vol. 80, no. 12, pp. 1745–1757, 1998. View at Google Scholar
  103. N. Boos, A. G. Nerlich, I. Wiest, K. Von Der Mark, and M. Aebi, “Immunolocalization of type X collagen in human lumbar intervertebral discs during ageing and degeneration,” Histochemistry and Cell Biology, vol. 108, no. 6, pp. 471–480, 1997. View at Publisher · View at Google Scholar · View at Scopus
  104. J. C. Gan, P. Ducheyne, E. J. Vresilovic, W. Swaim, and I. M. Shapiro, “Intervertebral disc tissue engineering I: characterization of the nucleus pulposus,” Clinical Orthopaedics and Related Research, no. 411, pp. 305–314, 2003. View at Google Scholar · View at Scopus
  105. K. Pelttari, A. Winter, E. Steck et al., “Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice,” Arthritis and Rheumatism, vol. 54, no. 10, pp. 3254–3266, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  106. Y.-J. Kim, H.-J. Kim, and G.-I. Im, “PTHrP promotes chondrogenesis and suppresses hypertrophy from both bone marrow-derived and adipose tissue-derived MSCs,” Biochemical and Biophysical Research Communications, vol. 373, no. 1, pp. 104–108, 2008. View at Publisher · View at Google Scholar · View at PubMed
  107. I. Sekiya, B. L. Larson, J. T. Vuoristo, R. L. Reger, and D. J. Prockop, “Comparison of effect of BMP-2, -4, and -6 on in vitro cartilage formation of human adult stem cells from bone marrow stroma,” Cell and Tissue Research, vol. 320, no. 2, pp. 269–276, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  108. F. Franceschi, U. G. Longo, L. Ruzzini, A. Marinozzi, N. Maffulli, and V. Denaro, “Simultaneous arthroscopic implantation of autologous chondrocytes and high tibial osteotomy for tibial chondral defects in the varus knee,” Knee, vol. 15, no. 4, pp. 309–313, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  109. W. S. Khan and U. G. Longo, “ACI and MACI procedures for cartilage repair utilise mesenchymal stem cells rather than chondrocytes,” Medical Hypotheses, vol. 77, no. 2, p. 309, 2011. View at Publisher · View at Google Scholar · View at PubMed
  110. U. G. Longo, F. Forriol, N. Maffulli, and V. Denaro, “Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage,” Osteoarthritis and Cartilage, vol. 18, no. 7, p. 1001, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  111. U. G. Longo, A. Berton, S. Alexander, N. Maffulli, A. L. Wallace, and V. Denaro, “Biological resurfacing for early osteoarthritis of the shoulder,” Sports Medicine and Arthroscopy Review, vol. 19, no. 4, pp. 380–394, 2011. View at Publisher · View at Google Scholar · View at PubMed
  112. C. Becher, A. Driessen, T. Hess, U. G. Longo, N. Maffulli, and H. Thermann, “Microfracture for chondral defects of the talus: maintenance of early results at midterm follow-up,” Knee Surgery, Sports Traumatology, Arthroscopy, vol. 18, no. 5, pp. 656–663, 2010. View at Publisher · View at Google Scholar · View at PubMed
  113. F. Forriol, U. G. Longo, E. Alvarez et al., “Scanty integration of osteochondral allografts cryopreserved at low temperatures with dimethyl sulfoxide,” Knee Surgery, Sports Traumatology, Arthroscopy, vol. 19, no. 7, pp. 1184–1191, 2011. View at Publisher · View at Google Scholar · View at PubMed
  114. U. G. Longo, F. Franceschi, L. Ruzzini, C. Rabitti, M. Nicola, and V. Denaro, “Foreign-body giant-cell reaction at the donor site after autologous osteochondral transplant for cartilaginous lesion. A case report,” Journal of Bone and Joint Surgery A, vol. 91, no. 4, pp. 945–949, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus