Skip to main content
SpringerLink
Log in

Regeneration potential and mechanism of bone marrow mesenchymal stem cell transplantation for treating intervertebral disc degeneration

  • Review Article
  • Published:
Journal of Orthopaedic Science

Abstract

Intervertebral disc degeneration is a primary cause of low back pain and has a high societal cost. The pathological mechanism by which the intervertebral disc degenerates is largely unknown. Cell-based therapy especially using bone marrow mesenchymal stem cells as seeds for transplantation, although still in its infancy, is proving to be a promising, realistic approach to intervertebral disc regeneration. This article reviews current advances regarding regeneration potential in both the in vivo and vitro studies of bone marrow mesenchymal stem cell-based therapy and discusses the up-to-date regeneration mechanisms of stem cell transplantation for treating intervertebral disc degeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pye SR, Reid DM, Smith R, Adams JE, Nelson K, Silman AJ, et al. Radiographic features of lumbar disc degeneration and self-reported back pain. J Rheumatol 2004;31:753–758.

    PubMed  Google Scholar 

  2. Hoyland JA, Le Maitre CL, Freemont AJ. Investigation of the role of IL-1 and TNF in matrix degradation in the intervertebral disc. Rheumatology 2008;47:809–814.

    Article  CAS  PubMed  Google Scholar 

  3. Miller JA, Schmatz C, Schultz AB. Lumbar disc degeneration: correlation with age, sex, and spine level in 600 autopsy specimens. Spine 1988;13:173–178.

    Article  CAS  PubMed  Google Scholar 

  4. Le Maitre CL, Freemont AJ, Hoyland JA. Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J Pathol 2004;204:47–54.

    Article  PubMed  CAS  Google Scholar 

  5. Le Maitre CL, Freemont AJ, Hoyland JA. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration. Arthritis Res Ther 2007;9:R45.

    Article  PubMed  CAS  Google Scholar 

  6. Richardson SM, Knowles R, Tyler J, Mobasheri A, Hoyland JA. Expression of glucose transporters GLUT-1, GLUT-3, GLUT-9 and HIF-1α in normal and degenerate human intervertebral disc. Histochem Cell Biol 2008;129:503–511.

    Article  CAS  PubMed  Google Scholar 

  7. Zhao CQ, Wang LM, Jiang LS, Dai LY. The cell biology of intervertebral disc aging and degeneration. Ageing Res Rev 2007;6:247–261.

    Article  PubMed  Google Scholar 

  8. Kim KW, Chung HN, Ha KY, Lee JS, Kim YY. Senescence mechanisms of nucleus pulposus chondrocytes in human intervertebral discs. Spine J 2009;9:658–666.

    Article  PubMed  Google Scholar 

  9. Sobajima S, Vadala G, Shimer A, Kim JS, Gilbertson LG, Kang JD. Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J 2008;8:888–896.

    Article  PubMed  Google Scholar 

  10. Yasuma T, Koh S, Okamura T, Yamauchi Y. Histological changes in aging lumbar intervertebral discs: their role in protrusions and prolapses. J Bone Joint Surg Am 1990;72:220–229.

    CAS  PubMed  Google Scholar 

  11. Thompson RE, Pearcy MJ, Downing KJ, Manthey BA, Parkinson IH, Fazzalari NL. Disc lesions and the mechanics of the intervertebral joint complex. Spine 2000;25:3026–3035.

    Article  CAS  PubMed  Google Scholar 

  12. Gruber HE, Ingram JA, Norton HJ, Hanley EN. Senescence in cells of the aging and degenerating intervertebral disc: immunolocalization of senescence-associated beta-galactosidase in human and sand rat discs. Spine 2007;32:321–327.

    Article  PubMed  Google Scholar 

  13. Kaneyama S, Nishida K, Takada T, Suzuki T, Shimomura T, Maeno K, et al. Fas ligand expression on human nucleus pulposus cells decreases with disc degeneration processes. J Orthop Sci 2008;13:130–135.

    Article  CAS  PubMed  Google Scholar 

  14. Peng B, Hao J, Hou S, Wu W, Jiang D, Fu X, et al. Possible pathogenesis of painful intervertebral disc degeneration. Spine 2006;31:560–566.

    Article  PubMed  Google Scholar 

  15. Richardson SM, Walker RV, Parker S, Rhodes NP, Hunt JA, Freemont AJ, et al. Intervertebral disc cell-mediated mesenchymal stem cell differentiation. Stem Cells 2006;24:707–716.

    Article  CAS  PubMed  Google Scholar 

  16. Yoon ST, Patel NM. Molecular therapy of the intervertebral disc. Eur Spine J 2006;15:S379–S388.

    Article  PubMed  Google Scholar 

  17. Zhang Y, Markova D, Im HJ, Hu W, Thonar EJ, He TC, et al. Primary bovine intervertebral disc cells transduced with adenovirus overexpressing 12 BMPs and Sox9 maintain appropriate phenotype. Am J Phys Med Rehabil 2009;88:455–463.

    Article  PubMed  Google Scholar 

  18. Masuda K. Biological repair of the degenerated intervertebral disc by the injection of growth factors. Eur Spine J 2008;17:441–451.

    Article  PubMed  Google Scholar 

  19. Masuda K, An HS. Prevention of disc degeneration with growth factors. Eur Spine J 2006;15:S422–S432.

    Article  PubMed  Google Scholar 

  20. Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, et al. Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine 2005;30:2379–2387.

    Article  PubMed  Google Scholar 

  21. Kuh SU, Zhu Y, Li J, Tsai KJ, Fei Q, Hutton WC, et al. A comparison of three cell types as potential candidates for intervertebral disc therapy: annulus fibrosus cells, chondrocytes, and bone marrow derived cells. Joint Bone Spine 2009;76:70–74.

    Article  CAS  PubMed  Google Scholar 

  22. Gorensek M, Jaksimovic C, Kregar-Velikonja N, Gorensek M, Knezevic M, Jeras M, et al. Nucleus pulposus repair with cultured autologous elastic cartilage derived chondrocytes. Cell Mol Biol Lett 2004;9:363–373.

    PubMed  Google Scholar 

  23. Nishimura K, Mochida J. Percutaneous reinsertion of the nucleus pulposus: an experimental study. Spine 1998;23:1531–1539.

    Article  CAS  PubMed  Google Scholar 

  24. Nomura T, Mochida J, Okuma M, Nishimura K, Sakabe K. Nucleus pulposus allograft retards intervertebral disc degeneration. Clin Orthop 2001;389:94–101.

    Article  PubMed  Google Scholar 

  25. Iwashina T, Mochida J, Sakai D, Yamamoto Y, Miyazaki T, Ando K, et al. Feasibility of using a human nucleus pulposus cell line as a cell source in cell transplantation therapy for intervertebral disc degeneration. Spine 2006;31:1177–1186.

    Article  PubMed  Google Scholar 

  26. Sakai D, Mochida J, Yamamoto Y, Toh E, Iwashina T, Miyazaki T, et al. Immortalization of human nucleus pulposus cells by a recombinant SV40 adenovirus vector: establishment of a novel cell line for the study of human nucleus pulposus cells. Spine 2004;29:1515–1523.

    Article  PubMed  Google Scholar 

  27. Sheikh H, Zakharian K, De La Torre RP, Facek C, Vasquez A, Chaudhry GR, et al. In vivo intervertebral disc regeneration using stem cell-derived chondroprogenitors. J Neurosurg Spine 2009;10:265–272.

    Article  PubMed  Google Scholar 

  28. Meisel HJ, Siodla V, Ganey T, Minkus Y, Hutton WC, Alasevic OJ. Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc. Biomol Eng 2007;24:5–21.

    Article  CAS  PubMed  Google Scholar 

  29. Meisel HJ, Ganey T, Hutton WC, Libera J, Minkus Y, Alasevic O. Clinical experience in cell-based therapeutics: intervention and outcome. Eur Spine J 2006;15:S397–405.

    Article  PubMed  Google Scholar 

  30. Hohaus C, Ganey TM, Minkus Y, Meisel HJ. Cell transplantation in lumbar spine disc degeneration disease. Eur Spine J 2008;17:492–503.

    Article  PubMed  Google Scholar 

  31. Anderson DG, Risbud MV, Shapiro IM, Vaccaro AR, Albert TJ. Cell-based therapy for disc repair. Spine J 2005;5:297S–303S.

    Article  PubMed  Google Scholar 

  32. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, Mclntosh K, Patil S, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002;30:42–48.

    Article  PubMed  Google Scholar 

  33. Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K, et al. Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 2003;24:3531–3541.

    Article  CAS  PubMed  Google Scholar 

  34. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WWK, Gordon PL, Neel M, et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 1999;5:309–313.

    Article  CAS  PubMed  Google Scholar 

  35. Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 2003;31:890–896.

    Article  PubMed  CAS  Google Scholar 

  36. Leung VY, Chan D, Cheung KM. Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction. Eur Spine J 2006;15:S406–S413.

    Article  PubMed  Google Scholar 

  37. Hoogendoorn RJW, Lu ZF, Kroeze RJ, Bank RA, Wuisman PI, Helder MN. Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future. J Cell Mol Med 2008;12:2205–2216.

    Article  CAS  PubMed  Google Scholar 

  38. Jim JJ, Noponen-Hietala N, Cheung KM, Ott J, Karppinen J, Sahraravand A, et al. The TRP2 allele of COL9A2 is an age-dependent risk factor for the development and severity of intervertebral disc degeneration. Spine 2005;30:2735–2742.

    Article  PubMed  Google Scholar 

  39. Noponen-Hietala N, Virtanen I, Karttunen R, Schwenke S, Jakkula E, Li H, et al. Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica. Pain 2005;114:186–194.

    Article  CAS  PubMed  Google Scholar 

  40. Semba K, Araki K, Li Z, Matsumoto K, Suzuki M, Nakagata N, et al. A novel murine gene, sickle tail, linked to the Danforth’s short tail locus, is required for normal development of the intervertebral disc. Genetics 2006;172:445–456.

    Article  CAS  PubMed  Google Scholar 

  41. Sethe S, Scutt A, Stolzing A. Aging of mesenchymal stem cells. Ageing Res Rev 2006;5:91–116.

    Article  CAS  PubMed  Google Scholar 

  42. Bellantuono I, Aldahmash A, Kassem M. Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss. Biochim Biophys Acta 2009;1792:364–370.

    CAS  PubMed  Google Scholar 

  43. Ryan JM, Barry FP, Murphy JM, Mahon BP. Mesenchymal stem cells avoid allogeneic rejection. J Inflamm (Lond) 2005;2:8.

    Article  CAS  Google Scholar 

  44. Gaetani P, Torre ML, Klinger M, Faustini M, Crovato F, Bucco M, et al. Adipose-derived stem cell therapy for Intervertebral disc regeneration: an in vitro reconstructed tissue in alginate capsules. Tissue Eng Part A 2008;14:1415–1423.

    Article  CAS  PubMed  Google Scholar 

  45. Ganey T, Hutton WC, Moseley T, Hedrick M, Meisel H. Intervertebral disc repair using adipose tissue-derived stem and regenerative cells: experiments in a canine model. Spine 2009;34:2297–2304.

    Article  PubMed  Google Scholar 

  46. Vadalà, G, Sobajima S, Lee JY, Huard J, Denaro V, Kang J, et al. In vitro interaction between muscle-derived stem cells and nucleus pulposus cells. Spine J 2008;8:804–809.

    Article  PubMed  Google Scholar 

  47. Murrell W, Sanford E, Anderberg L, Cavanagh B, Mackay-Sim A. Olfactory stem cells can be induced to express chondrogenic phenotype in a rat intervertebral disc injury model. Spine J 2009;9:585–594.

    Article  PubMed  Google Scholar 

  48. Gilchrist CL, Chen J, Richardson WJ, Loeser RF, Setton LA. Functional integrin subunits regulating cell-matrix interactions in the intervertebral disc. J Orthop Res 2007;25:829–840.

    Article  CAS  PubMed  Google Scholar 

  49. Henriksson HB, Thornemo M, Karlsson C, Hägg O, Junevik K, Lindahl A, et al. Identification of cell proliferation zones, progenitor cells and a potential stem cell niche in the intervertebral disc region: a study in four species. Spine 2009;34:2278–2287.

    Article  PubMed  Google Scholar 

  50. Moore KA, Lemischka IR. Stem cells and their niches. Science 2006;311:1880–1885.

    Article  CAS  PubMed  Google Scholar 

  51. Risbud MV, Guttapalli A, Tsai TT, Lee JY, Danielson KG, Vaccaro AR, et al. Evidence for skeletal progenitor cells in the degenerate human intervertebral disc. Spine 2007;32:2537–2544.

    Article  PubMed  Google Scholar 

  52. Zhao J, Zhang N, Prestwich GD, Wen XJ. Recruitment of endogenous stem cells for tissue repair. Macromol Biosci 2008;8:836–842.

    Article  CAS  PubMed  Google Scholar 

  53. Chen WH, Liu HY, Lo WC, Wu SC, Chi CH, Chang HY, et al. Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biomaterials 2009;30:5523–5533.

    Article  CAS  PubMed  Google Scholar 

  54. Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, et al. Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 2004;32:430–434.

    Article  PubMed  Google Scholar 

  55. Zhang YG, Guo X, Xu P, Kang LL, Li J. Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans. Clin Orthop 2005;430:219–226.

    PubMed  Google Scholar 

  56. Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K, et al. Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res 2008;26:589–600.

    Article  CAS  PubMed  Google Scholar 

  57. Yang F, Leung VY, Luk KD, Chan D, Cheung KM. Mesenchymal stem cells arrest intervertebral disc degeneration through chondrocytic differentiation and stimulation of endogenous cells. Mol Ther 2009;7:1959–1966.

    Article  CAS  Google Scholar 

  58. Henriksson HB, Svanvik T, Jonsson M, Hagman M, Horn M, Lindahl A, et al. Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model. Spine 2009;34:141–148.

    Article  PubMed  Google Scholar 

  59. Wei A, Tao H, Chung SA, Brisby H, Ma DD, Diwan AD. The fate of transplanted xenogeneic bone marrow-derived stem cells in rat intervertebral discs. J Orthop Res 2009;27:374–379.

    Article  PubMed  Google Scholar 

  60. Bao JP, Wu XT, Wang YT, Zhang FY. In vivo MR imaging tracking of iron oxide labeled autologous bone marrow mesenchymal stem cells following degenerated disc injection. J Southeast Univ Med Sci Ed 2008;27:166–170 (in Chinese).

    Google Scholar 

  61. Zhang Y, An HS, Tannoury C, Thonar EJ, Freedman MK, Anderson DG. Biological treatment for degenerative disc disease: implications for the field of physical medicine and rehabilitation. Am J Phys Med Rehabil 2008;87:694–702.

    Article  PubMed  Google Scholar 

  62. Haufe SM, Mork AR. Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev 2006;15:136–137.

    Article  PubMed  Google Scholar 

  63. Yoshikawa T, Ueda Y, Miyazaki K, Koizumi M, Takakura Y. Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine 2010;35:E475–E480.

    PubMed  Google Scholar 

  64. Le Maitre CL, Baird P, Freemont AJ, Hoyland JA. An in vitro study investigating the survival and phenotype of mesenchymal stem cells following injection into nucleus pulposus tissue. Arthritis Res Ther 2009;11:R20.

    Article  PubMed  CAS  Google Scholar 

  65. Yamamoto Y, Mochida J, Sakai D, Nakai T, Nishimura K, Kawada H, et al. Upregulation of the viability of nucleus pulposus cells by bone marrow-derived stromal cells: significance of direct cell-to-cell contact in coculture system. Spine 2004;29;1508–14.

    Article  PubMed  Google Scholar 

  66. Le Visage C, Kim SW, Tateno K, Sieber AN, Kostuik JP, Leong KW. Interaction of human mesenchymal stem cells with disc cells: changes in extracellular matrix biosynthesis. Spine 2006;31:2036–2042.

    Article  PubMed  Google Scholar 

  67. Yang SH, Wu CC, Shih TF, Sun YH, Lin FH. In vitro study on interaction between human nucleus pulposus cells and mesenchymal stem cells through paracrine stimulation. Spine 2008;33:1951–1957.

    Article  PubMed  Google Scholar 

  68. Watanabe T, Sakai D, Yamamoto Y, Iwashina T, Serigano K, Tamura F, et al. Human nucleus pulposus cells significantly enhanced biological properties in a coculture system with direct cell-to-cell contact with autologous mesenchymal stem cells. J Orthop Res 2010;28:623–630.

    CAS  PubMed  Google Scholar 

  69. Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 2000;28:875–884.

    Article  CAS  PubMed  Google Scholar 

  70. Richardson SM, Hughes N, Hunt JA, Freemont AJ, Hoyland JA. Human mesenchymal stem cell differentiation to NP-like cells in chitosan-glycerophosphate hydrogels. Biomaterials 2008;29:85–93.

    Article  CAS  PubMed  Google Scholar 

  71. Wuertz K, Godburn K, Neidlinger-Wilke C, Urban J, Latridis JC. Behavior of mesenchymal stem cells in the chemical microenvironment of the intervertebral disc. Spine 2008;33:1843–1849.

    Article  PubMed  Google Scholar 

  72. Vadalà G, Studer RK, Sowa G, Spiezia F, Iucu C, Denaro V, et al. Coculture of bone marrow mesenchymal stem cells and nucleus pulposus cells modulate gene expression profile without cell fusion. Spine 2008;33:870–876.

    Article  PubMed  Google Scholar 

  73. Bron JL, Helder MN, Meisel HJ, Van-Royen BJ, Smit TH. Repair, regenerative and supportive therapies of the annulus fibrosus: achievements and challenges. Eur Spine J 2009;18:301–313.

    Article  PubMed  Google Scholar 

  74. Hiyama A, Mochida J, Sakai D. Stem cell applications in intervertebral disc repair. Cell Mol Biol 2008;54:24–32.

    CAS  PubMed  Google Scholar 

  75. Kimelman N, Oskouian RJ, Zilberman Y, Pelled G, Gazit Z, Gazit D. Genetically engineered adult stem cells and hybrid scaffolds as a platform for intervertebral disc regeneration. Mol Ther 2006;13:S175–S176.

    Article  Google Scholar 

  76. Ryan JM, Barry F, Murphy JM, Mahon BP. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin Exp Immunol 2007;149:353–363.

    Article  CAS  PubMed  Google Scholar 

  77. Haynesworth SE, Baber MA, Caplan AI. Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: effects of dexamethasone and IL-1 alpha. J Cell Physiol 1996;166:585–592.

    Article  CAS  PubMed  Google Scholar 

  78. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006;98:1076–1084.

    Article  CAS  PubMed  Google Scholar 

  79. Masuda K, Oegema TR Jr, An HS. Growth factors and treatment of intervertebral disc degeneration. Spine 2004;29:2757–2769.

    Article  PubMed  Google Scholar 

  80. Pratsinis H, Kletsas D. Growth factors in intervertebral disc homeostasis. Connect Tissue Res 2008;49:273–276.

    Article  CAS  PubMed  Google Scholar 

  81. Gruber HE, Fisher EC Jr, Desai B, Stasky AA, Hoelscher G, Hanley EN. Human intervertebral disc cells from the annulus: three-dimensional culture in agarose or alginate and responsiveness to TGF-β1. Exp Cell Res 1997;235:13–21.

    Article  CAS  PubMed  Google Scholar 

  82. Thompson JP, Oegema TR Jr, Bradford DS. Stimulation of mature canine intervertebral disc by growth factors. Spine 1991;16:253–260.

    Article  CAS  PubMed  Google Scholar 

  83. Osada R, Ohshima H, Ishihara H, Yudoh K, Sakai K, Matsui H, et al. Autocrine/paracrine mechanism of insulin-like growth factor-1 secretion, and the effect of insulin-like growth factor-1 on proteoglycan synthesis in bovine intervertebral discs. J Orthop Res 1996;14:690–699.

    Article  CAS  PubMed  Google Scholar 

  84. Gruber HE, Norton HJ, Hanley EN Jr. Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro. Spine 2000;25:2153–2157.

    Article  CAS  PubMed  Google Scholar 

  85. Pratsinis H, Kletsas D. PDGF, bFGF and IGF-I stimulate the proliferation of intervertebral disc cells in vitro via the activation of the ERK and Akt signaling pathways. Eur Spine J 2007;16:1858–1866.

    Article  PubMed  Google Scholar 

  86. Li X, Leo BM, Beck G, Balian G, Anderson DG. Collagen and proteoglycan abnormalities in the GDF-5-deficient mice and molecular changes when treating disk cells with recombinant growth factor. Spine 2004;29:2229–2234.

    Article  PubMed  Google Scholar 

  87. Masuda K, Takegami K, An H, Kumano F, Chiba K, Andersson GB, et al. Recombinant osteogenic protein-1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells cultured in alginate beads. J Orthop Res 2003;21:922–930.

    Article  CAS  PubMed  Google Scholar 

  88. Tim Yoon S, Su Kim K, Li J, Soo Park J, Akamaru T, Elmer WA, Hutton WC. The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro. Spine 2003;28:1773–1780.

    Article  CAS  PubMed  Google Scholar 

  89. Gilbertson L, Ahn SH, Teng PN, Studer RK, Niyibizi C, Kang JD. The effects of recombinant human bone morphogenetic protein-2, recombinant human bone morphogenetic protein-12, and adenoviral bone morphogenetic protein-12 on matrix synthesis in human annulus fibrosis and nucleus pulposus cells. Spine J 2008;8:449–456.

    Article  PubMed  Google Scholar 

  90. Mochida J. New strategies of disc repair; novel preclinical trials. J Orthop Sci 2005;10:112–118.

    Article  PubMed  Google Scholar 

  91. Yan HS, Wu XT, Wang YT, Shao JS, Cao Y, Bao JP, et al. The rise and fall of the trophic and differentiated effects in cell therapy for regeneration of degenerative intervertebral discs. Chin J Exp Surg 2009;26:125–127.

    Google Scholar 

  92. Wei A, Brisby H, Chung SA, Diwan AD. Bone morphogenetic protein-7 protects human intervertebral disc cells in vitro from apoptosis. Spine J 2008;8:466–474.

    Article  PubMed  Google Scholar 

  93. Zhao CQ, Wang LM, Jiang LS, Dai LY. Programmed cell death in intervertebral disc degeneration. Apoptosis 2006;11:2079–2088.

    Article  PubMed  Google Scholar 

  94. Broker LE, Kruyt FA, Giaccone G. Cell death independent of caspases: a review. Clin Cancer Res 2005;11:3155–3162.

    Article  PubMed  Google Scholar 

  95. Park JB, Lee JK, Park SJ, Kim KW, Riew KD. Mitochondrial involvement in fas-mediated apoptosis of human lumbar disc cells. J Bone Joint Surg Am 2005;87:1338–1342.

    Article  PubMed  Google Scholar 

  96. Ariga K, Yonenobu K, Nakase T, Hosono N, Okuda S, Meng W, et al. Mechanical stress-induced apoptosis of endplate chondrocytes in organ-cultured mouse intervertebral discs: an ex vivo study. Spine 2003;28:1528–1533.

    Article  PubMed  Google Scholar 

  97. Tschoeke SK, Hellmuth M, Hostmann A, Robinson Y, Ertel W, Oberholzer A, et al. Apoptosis of human intervertebral discs after trauma compares to degenerated discs involving both receptor-mediated and mitochondrial-dependent pathways. J Orthop Res 2008;26:999–1006.

    Article  CAS  PubMed  Google Scholar 

  98. Park JB, Park IC, Park SJ, Jin HO, Lee JK, Riew KD. Antiapoptotic effects of caspase inhibitors on rat intervertebral disc cells. J Bone Joint Surg Am 2006;88:771–779.

    Article  PubMed  Google Scholar 

  99. Tapp H, Deepe R, Ingram JA, Yarmola EG, Bubb MR, Hanley EN Jr, et al. Exogenous thymosin beta(4) prevents apoptosis in human intervertebral annulus cells in vitro. Biotech Histochem 2009;84:287–294.

    Article  CAS  PubMed  Google Scholar 

  100. Kang Y, Liao WM, Sheng PY, Zhang LJ, Yuan XW, Lei L, et al. Construction and identification of human bone morphogenetic protein-7 recombinant adeno-associated virus type 2 vector and its expression in bone mesenchymal stem cells. Zhonghua Wai Ke Za Zhi 2007;45:1279–1283 (in Chinese).

    PubMed  Google Scholar 

  101. Risbud MV, Guttapalli A, Stokes DG, Hawkins D, Danielson KG, Schaer TP, et al. Nucleus pulposus cells express HIF-1 alpha under normoxic culture conditions: a metabolic adaptation to the intervertebral disc microenvironment. J Cell Biochem 2006;98:152–159.

    Article  CAS  PubMed  Google Scholar 

  102. Zeng Y, Danielson KG, Albert TJ, Shapiro IM, Risbud MV. HIF-1 alpha is a regulator of galectin-3 expression in the intervertebral disc. J Bone Miner Res 2007;22:1851–1861.

    Article  CAS  PubMed  Google Scholar 

  103. Gruber HE, Ingram JA, Davis DE, Hanley EN Jr. Increased cell senescence is associated with decreased cell proliferation in vivo in the degenerating human annulus. Spine J 2009;9:210–215.

    Article  PubMed  Google Scholar 

  104. Roberts S, Evans EH, Kletsas D, Jaffray DC, Eisenstein SM. Senescence in human intervertebral discs. Eur Spine J 2006;15:S312–S316.

    Article  PubMed  Google Scholar 

  105. Zhou HW, Hou SX, Shang WL, Mei F. Effect of P16INK4a vs Fas on function of intervertebral disc. Chin J Exp Surg 2006;23:1505–1507.

    CAS  Google Scholar 

  106. Nakai T, Mochida J, Sakai D. Synergistic role of c-Myc and ERK1/2 in the mitogenic response to TGF beta-1 in cultured rat nucleus pulposus cells. Arthritis Res Ther 2008;10:R140.

    Article  PubMed  CAS  Google Scholar 

  107. Gruber HE, Hoelscher GL, Ingram JA, Bethea S, Hanley EN. IGF-1 rescues human intervertebral annulus cells from in vitro stress-induced premature senescence. Growth Factors 2008;26:220–225.

    Article  CAS  PubMed  Google Scholar 

  108. Niu CC, Yuan LJ, Lin SS, Chen LH, Chen WJ. Mesenchymal stem cell and nucleus pulposus cell coculture modulates cell profile. Clin Orthop 2009;467:3263–3272.

    Article  PubMed  Google Scholar 

  109. Lepperdinger G, Brunauer R, Jamnig A, Laschober G, Kassem M. Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies? Exp Gerontol 2008;43:1018–1023.

    Article  CAS  PubMed  Google Scholar 

  110. Momin EN, Vela G, Zaidi HA, Quiñones-Hinojosa A. The oncogenic potential of mesenchymal stem cells in the treatment of cancer: directions for future research. Curr Immunol Rev 2010;6:137–148.

    Article  CAS  PubMed  Google Scholar 

  111. Sakai D. Future perspectives of cell-based therapy for intervertebral disc disease. Eur Spine J 2008;17:S452–S458.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedics, Zhongda Hospital, Southeast University, 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, P. R. China

    Yun-Tao Wang, Xiao-Tao Wu & Feng Wang

Authors
  1. Yun-Tao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Tao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Feng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Wang, YT., Wu, XT. & Wang, F. Regeneration potential and mechanism of bone marrow mesenchymal stem cell transplantation for treating intervertebral disc degeneration. J Orthop Sci 15, 707–719 (2010). https://doi.org/10.1007/s00776-010-1536-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00776-010-1536-3

Keywords

Search

Navigation