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Use of Stem Cells for Regeneration of the Intervertebral Disc

  • Daisuke SakaiEmail author
  • Joji Mochida
Chapter

Abstract

The ability of a tissue to respond to stress or injury requires the involvement and functions of stem cells resident in tissue-specific microenvironmental niches. Aging has been shown to result in a decrease in stem cell number as well as loss of ability to maintain tissue homeostasis and regenerate lost tissue function. Therefore, it is of critical importance to identify stem/progenitor cell populations in different tissues, determine how these cells function in tissue homeostasis, and ascertain their potential utility in tissue engineering.

Keywords

Intervertebral Disc Nucleus Pulposus Disc Degeneration Annulus Fibrosus Nucleus Pulposus Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors are grateful to the staff of the Education and Research Support Center, Tokai University. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and a grant from AOSpine International and AO Foundation to D.S.

References

  1. Allon AA, Aurouer N, Yoo BB, Liebenberg EC, Buser Z, Lotz JC (2010) Structured coculture of stem cells and disc cells prevent disc degeneration in a rat model. Spine J 10:1089–1097PubMedCrossRefGoogle Scholar
  2. Bendtsen M, Bünger CE, Zou X, Foldager C, Jørgensen HS (2011) Autologous stem cell therapy maintains vertebral blood flow and contrast diffusion through the endplate in experimental intervertebral disc degeneration. Spine (Phila Pa 1976) 36:E373–E379CrossRefGoogle Scholar
  3. Bertolo A, Mehr M, Aebli N, Baur M, Ferguson SJ, Stoyanov JV (2012) Influence of different commercial scaffolds on the in vitro differentiation of human mesenchymal stem cells to nucleus pulposus-like cells. Eur Spine J 21:S826–S838PubMedCrossRefGoogle Scholar
  4. Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19:180–192PubMedCrossRefGoogle Scholar
  5. Blanco JF, Graciani IF, Sanchez-Guijo FM, Muntion S, Hernandez-Campo P, Santamaria C, Carrancio S, Barbado MV, Cruz G, Gutierrez-Cosio S, Herrero C, San Miguel JF, Brinon JG, del Canizo MC (2010) Isolation and characterization of mesenchymal stromal cells from human degenerated nucleus pulposus: comparison with bone marrow mesenchymal stromal cells from the same subjects. Spine (Phila Pa 1976) 35:2259–2265CrossRefGoogle Scholar
  6. Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E (2004) Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 118:635–648PubMedCrossRefGoogle Scholar
  7. Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641–650PubMedCrossRefGoogle Scholar
  8. Chen WH, Liu HY, Lo WC, Wu SC, Chi CH, Chang HY, Hsiao SH, Wu CH, Chiu WT, Chen BJ, Deng WP (2009) Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. Biomaterials 30:5523–5533PubMedCrossRefGoogle Scholar
  9. Choi EH, Park H, Park KS, Park KS, Kim BS, Han IB, Shin DA, Lee SH (2011) Effect of nucleus pulposus cells having different phenotypes on chondrogenic differentiation of adipose-derived stromal cells in a coculture system using porous membranes. Tissue Eng Part A 17:2445–2451PubMedCrossRefGoogle Scholar
  10. Chun HJ, Kim YS, Kim BK, Kim EH, Kim JH, Do BR, Hwang SJ, Hwang JY, Lee YK (2012) Transplantation of human adipose-derived stem cells in a rabbit model of traumatic degeneration of lumbar discs. World Neurosurg 78:364–371PubMedCrossRefGoogle Scholar
  11. Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, Berven S (2004) Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 32:430–434PubMedCrossRefGoogle Scholar
  12. Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Péault B (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313PubMedCrossRefGoogle Scholar
  13. Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 2:875–884CrossRefGoogle Scholar
  14. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMedCrossRefGoogle Scholar
  15. Driscoll TP, Nerurkar NL, Jacobs NT, Elliott DM, Mauck RL (2011) Fiber angle and aspect ratio influence the shear mechanics of oriented electrospun nanofibrous scaffolds. J Mech Behav Biomed Mater 4:1627–1636PubMedCrossRefGoogle Scholar
  16. Ehlicke F, Freimark D, Heil B, Dorresteijn A, Czermak P (2010) Intervertebral disc regeneration: influence of growth factors on differentiation of human mesenchymal stem cells (hMSC). Int J Artif Organs 33:244–252PubMedGoogle Scholar
  17. Feng G, Yang X, Shang H, Marks IW, Shen FH, Katz A, Arlet V, Laurencin CT, Li X (2010) Multipotential differentiation of human annulus fibrosus cells: an in vitro study. J Bone Joint Surg Am 92:675–685PubMedCrossRefGoogle Scholar
  18. Feng G, Jin X, Hu J, Ma H, Gupte MJ, Liu H, Ma PX (2011a) Effects of hypoxias and scaffold architecture on rabbit mesenchymal stem cell differentiation toward a nucleus pulposus-like phenotype. Biomaterials 32:8182–8189PubMedCrossRefGoogle Scholar
  19. Feng G, Zhao X, Liu H, Zhang H, Chen X, Shi R, Liu X, Zhao X, Zhang W, Wang B (2011b) Transplantation of mesenchymal stem cells and nucleus pulposus cells in a degenerative disc model in rabbits: a comparison of 2 cell types as potential candidates for disc regeneration. J Neurosurg Spine 14:322–329PubMedCrossRefGoogle Scholar
  20. Gaetani P, Torre ML, Klinger M, Faustini M, Crovato F, Bucco M, Marazzi M, Chlapanidas T, Levi D, Tancioni F, Vigo D, Rodriguez y Baena R (2008) Adipose-derived stem cell therapy for intervertebral disc regeneration: an in vitro reconstructed tissue in alginate capsules. Tissue Eng Part A 14:1415–1423PubMedCrossRefGoogle Scholar
  21. Ganey T, Hutton WC, Moseley T, Hedrick M, Meisel HJ (2009) Intervertebral disc repair using adipose tissue-derived stem and regenerative cells: experiments in a canine model. Spine (Phila Pa 1976) 34:2297–2304CrossRefGoogle Scholar
  22. Haufe SM, Mork AR (2006) Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev 15:136–137PubMedCrossRefGoogle Scholar
  23. He F, Pei M (2012) Rejuvenation of nucleus pulposus cells using extracellular matrix deposited by synovium-derived stem cells. Spine (Phila Pa 1976) 37:459–469CrossRefGoogle Scholar
  24. Henriksson H, Thornemo M, Karlsson C, Hagg O, Junevik K, Lindahl A, Brisby H (2009) Identification of cell proliferation zones, progenitor cells and a potential stem cell niche in the intervertebral disc region: a study in four species. Spine (Phila Pa 1976) 34:2278–2287CrossRefGoogle Scholar
  25. Henriksson HB, Svala E, Skioldebrand E, Lindahl A, Brisby H (2011) Support of concept that migrating progenitor cells from stem cell niches contribute to normal regeneration of the adult mammal intervertebral disc: a descriptive study in the New Zealand white rabbit. Spine (Phila Pa 1976) 37:722–732CrossRefGoogle Scholar
  26. Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K, Tamura F, Sakai D (2008) Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res 26:589–600PubMedCrossRefGoogle Scholar
  27. Hoogendoorn RJ, Lu ZF, Kroeze RJ, Bank RA, Wuisman PI, Helder MN (2008) Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future. J Cell Mol Med 12:2205–2216PubMedCrossRefGoogle Scholar
  28. Kim DH, Kim SH, Heo SJ, Shin JW, Lee SW, Park SA, Shin JW (2009) Enhanced differentiation of mesenchymal stem cells into NP-like cells via 3D co-culturing with mechanical stimulation. J Biosci Bioeng 108:63–67PubMedCrossRefGoogle Scholar
  29. Korecki CL, Taboas JM, Tuan RS, Iatridis JC (2010) Notochordal cell conditioned medium stimulates mesenchymal stem cell differentiation toward a young nucleus pulposus phenotype. Stem Cell Res Ther 1:18PubMedCrossRefGoogle Scholar
  30. Le Maitre CL, Baird P, Freemont AJ, Hoyland JA (2009) An in vitro study investigating the survival and phenotype of mesenchymal stem cells following injection into nucleus pulposus tissue. Arthritis Res Ther 11:R20PubMedCrossRefGoogle Scholar
  31. Leung VY, Chan D, Cheung KM (2006) Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction. Eur Spine J 15(Suppl 3):S406–S413PubMedCrossRefGoogle Scholar
  32. Li X, Lee JP, Balian G, Greg AD (2005) Modulation of chondrocytic properties of fat-derived mesenchymal cells in co-cultures with nucleus pulposus. Connect Tissue Res 46:75–82PubMedCrossRefGoogle Scholar
  33. Liu LT, Huang B, Li CQ, Zhuang Y, Wang J, Zhou Y (2011) Characteristics of stem cells derived from the degenerated human intervertebral disc cartilage endplate. PLoS One 6:e26285PubMedCrossRefGoogle Scholar
  34. Lu ZF, Zandieh Doulabi B, Wuisman PI, Bank RA, Helder MN (2007) Differentiation of adipose stem cells by nucleus pulposus cells: configuration effect. Biochem Biophys Res Commun 359:991–996PubMedCrossRefGoogle Scholar
  35. Luo W, Xiong W, Qiu M, Lv Y, Li Y, Li F (2011) Differentiation of mesenchymal stem cells toward a nucleus pulposus-like phenotype utilizing simulated microgravity in vitro. J Huazhong Univ Sci Technolog Med Sci 31:199–203PubMedCrossRefGoogle Scholar
  36. Melrose J, Smith SM, Fuller ES, Young AA, Roughley PJ, Dart A, Little CB (2007) Biglycan and fibromodulin fragmentation correlates with temporal and spatial annular remodelling in experimentally injured ovine intervertebral discs. Eur Spine J 16:2193–2205PubMedCrossRefGoogle Scholar
  37. Meyerrose T, Olson S, Pontow S, Kalomoiris S, Jung Y, Annett G, Bauer G, Nolta JA (2010) Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors. Adv Drug Deliv Rev 62:1167–1174PubMedCrossRefGoogle Scholar
  38. Miyamoto T, Muneta T, Tabuchi T, Matsumoto K, Saito H, Tsuji K, Sekiya I (2010) Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits. Arthritis Res Ther 12:R206PubMedCrossRefGoogle Scholar
  39. Nesti LJ, Li WJ, Shanti RM, Jiang YJ, Jackson W, Freedman BA, Kuklo TR, Giuliani JR, Tuan RS (2008) Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous scaffold (HANFS) amalgam. Tissue Eng Part A 14:1527–1537PubMedCrossRefGoogle Scholar
  40. Orozco L, Soler R, Morera C, Alberca M, Sánchez A, García-Sancho J (2011) Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 92:822–828PubMedCrossRefGoogle Scholar
  41. Purmessur D, Schek RM, Abbott RD, Ballif BA, Godburn KE, Iatridis JC (2011) Notochordal conditioned media from tissue increases proteoglycan accumulation and promotes a healthy nucleus pulposus phenotype in human mesenchymal stem cells. Arthritis Res Ther 13:R81PubMedCrossRefGoogle Scholar
  42. Richardson SM, Walker RV, Parker S, Rhodes NP, Hunt JA, Freemont AJ, Hoyland JA (2006) Intervertebral disc cell-mediated mesenchymal stem cell differentiation. Stem Cells 24:707–716PubMedCrossRefGoogle Scholar
  43. Risbud MV, Albert TJ, Guttapalli A, Vresilovic EJ, Hillibrand AS, Vaccaro AR, Shapiro IM (2004) Differentiation of mesenchymal stem cells towards a nucleus pulposus-like phenotype in vitro: implications for cell-based transplantation therapy. Spine (Phila Pa 1976) 29:2627–2632CrossRefGoogle Scholar
  44. Risbud MV, Guttapalli A, Tsai TT, Lee JY, Danielson KG, Vaccaro AR, Albert TJ, Gazit Z, Gazit D, Shapiro IM (2007) Evidence for skeletal progenitor cells in the degenerate human intervertebral disc. Spine (Phila Pa 1976) 32:2537–2544CrossRefGoogle Scholar
  45. Ruan D, Zhang Y, Wang D, Zhang C, Wu J, Wang C, Shi Z, Xin H, Xu C, Li H, He Q (2012) Differentiation of human Wharton’s jelly cells toward nucleus pulposus-like cells after coculture with nucleus pulposus cells in vitro. Tissue Eng Part A 18:167–175PubMedCrossRefGoogle Scholar
  46. Sakai D (2011) Stem cell regeneration of the intervertebral disk. Orthop Clin North Am 42:555–562, viii–ix. ReviewPubMedCrossRefGoogle Scholar
  47. Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K, Nakai T, Ando K, Hotta T (2003) Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 24:3531–3541PubMedCrossRefGoogle Scholar
  48. Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T (2005) Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: potential and limitations for stem cell therapy in disc regeneration. Spine (Phila Pa 1976) 30:2379–2387CrossRefGoogle Scholar
  49. Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M, Nakai T, Ando K, Hotta T (2006) Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 27:335–345PubMedCrossRefGoogle Scholar
  50. Sakai D, Nakamura Y, Nakai T, Mishima T, Kato S, Grad S, Alini M, Risbud M, Chan D, Cheah K, Yamamura K, Masuda K, Okano H, Ando K, Mochida J (2012) Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc. Nat Commun 3:1264PubMedCrossRefGoogle Scholar
  51. See EY, Toh SL, Goh JC (2011) Simulated intervertebral disc-like assembly using bone marrow-derived mesenchymal stem cell sheets and silk scaffolds for annulus fibrosus regeneration. J Tissue Eng Regen Med. doi: 10.1002/term.457 PubMedGoogle Scholar
  52. Serigano K, Sakai D, Hiyama A, Tamura F, Tanaka M, Mochida J (2010) Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. J Orthop Res 28:1267–1275PubMedCrossRefGoogle Scholar
  53. Sobajima S, Vadalà G, Shimer A, Kim JS, Gilbertson LG, Kang JD (2008) Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J 8:888–896PubMedCrossRefGoogle Scholar
  54. Steck E, Bertram H, Abel R, Chen B, Winter A, Richter W (2005) Induction of intervertebral disc-like cells from adult mesenchymal stem cells. Stem Cells 23:403–411PubMedCrossRefGoogle Scholar
  55. Stoyanov JV, Gantenbein-Ritter B, Bertolo A, Aebli N, Baur M, Alini M, Grad S (2011) Role of hypoxia and growth and differentiation factor-5 on differentiation of human mesenchymal stem cells toward intervertebral nucleus pulposus-like cells. Eur Cell Mater 21:533–547PubMedGoogle Scholar
  56. Strassburg S, Richardson SM, Freemont AJ, Hoyland JA (2010) Co-culture induces mesenchymal stem cell differentiation and modulation of the degenerate human nucleus pulposus cell phenotype. Regen Med 5:701–711PubMedCrossRefGoogle Scholar
  57. Tzaan WC, Chen HC (2011) Investigating the possibility of intervertebral disc regeneration induced by granulocyte colony stimulating factor-stimulated stem cells in rats. Adv Orthop 2011:602089. Epub 2010 Nov 21PubMedGoogle Scholar
  58. Vadalà G, Studer RK, Sowa G, Spiezia F, Iucu C, Denaro V, Gilbertson LG, Kang JD (2008) Coculture of bone marrow mesenchymal stem cells and nucleus pulposus cells modulate gene expression profile without cell fusion. Spine (Phila Pa 1976) 33:870–876CrossRefGoogle Scholar
  59. Vadalà G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD (2012) Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med 6:348–355. doi: 10.1002/term.433 PubMedCrossRefGoogle Scholar
  60. Wei A, Chung SA, Tao H, Brisby H, Lin Z, Shen B, Ma DD, Diwan AD (2009a) Differentiation of rodent bone marrow mesenchymal stem cells into intervertebral disc-like cells following coculture with rat disc tissue. Tissue Eng Part A 15:2581–2595PubMedCrossRefGoogle Scholar
  61. Wei A, Tao H, Chung SA, Brisby H, Ma DD, Diwan AD (2009b) The fate of transplanted xenogeneic bone marrow-derived stem cells in rat intervertebral discs. J Orthop Res 27:374–379PubMedCrossRefGoogle Scholar
  62. Wuertz K, Godburn K, Neidlinger-Wilke C, Urban J, Iatridis JC (2008) Behavior of mesenchymal stem cells in the chemical microenvironment of the intervertebral disc. Spine (Phila Pa 1976) 33:1843–1849CrossRefGoogle Scholar
  63. Yamamoto Y, Mochida J, Sakai D, Nakai T, Nishimura K, Kawada H, Hotta T (2004) 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 (Phila Pa 1976) 29:1508–1514CrossRefGoogle Scholar
  64. Yang H, Wu J, Liu J, Ebraheim M, Castillo S, Liu X, Tang T, Ebraheim NA (2010) Transplanted mesenchymal stem cells with pure fibrinous gelatin–transforming growth factor-β1 decrease rabbit intervertebral disc degeneration. Spine J 10:802–810PubMedCrossRefGoogle Scholar
  65. Yoshikawa T, Ueda Y, Miyazaki K, Koizumi M, Takakura Y (2010) Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine (Phila Pa 1976) 35:E475–E480Google Scholar
  66. Zhang YG, Guo X, Xu P, Kang LL, Li J (2005) Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans. Clin Orthop Relat Res 430:219–226PubMedCrossRefGoogle Scholar

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© Springer-Verlag Wien 2014

Authors and Affiliations

  1. 1.Department of Orthopaedic Surgery, Surgical Science, Research Center for Regenerative MedicineTokai University School of MedicineIsehara, KanagawaJapan

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