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Future perspectives of cell-based therapy for intervertebral disc disease

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Abstract

Intervertebral disc degeneration is a primary cause of low back pain and has a high societal cost. Research on cell-based therapies for intervertebral disc disease is emerging, along with the interest in biological therapy to treat disc disease without reducing the mobility of the spinal motion segment. Results from animal models have shown promising results under limited conditions; however, future studies are needed to optimise efficacy, methodology, and safety. To advance research on cell-based therapy for intervertebral disc disease, a better understanding of the phenotype and differentiation of disc cells and of their microenvironment is essential. This article reviews current concepts in cell-based therapy for intervertebral disc disease, with updates on potential cell sources tested primarily using animal models, and discusses the hurdles to clinical application. Future perspectives for cell-based therapies for intervertebral disc disease are also discussed.

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References

  1. An HS, Thonar EJ, Masuda K (2003) Biological repair of intervertebral disc. Spine 28:S86–S92

    Article  PubMed  Google Scholar 

  2. Anderson DG, Albert TJ, Fraser JK, Risbud M, Wuisman P, Meisel HJ, Tannoury C, Shapiro I, Vaccaro AR (2005) Cellular therapy for disc degeneration. Spine 30:S14–S19

    Article  PubMed  Google Scholar 

  3. Antoniou J, Steffen T, Nelson F, Winterbottom N, Hollander AP, Poole RA, Aebi M, Alini M (1996) The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest 98:996–1003

    Article  PubMed  CAS  Google Scholar 

  4. Alini M, Roughley PJ, Antoniou J, Stoll T, Aebi M (2002) A biological approach to treating disc degeneration: not for today, but may be for tomorrow. Eur Spine J 11:S215–S220

    PubMed  Google Scholar 

  5. Buckwalter JA (1995) Aging and degeneration of the human intervertebral disc. Spine 20:1307–1314

    PubMed  CAS  Google Scholar 

  6. 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 32:430–434

    Article  PubMed  Google Scholar 

  7. Frymoyer JW, Cats-Baril WL (1991) An overview of the incidence and costs of low back pain. Orthop Clin North Am 22:263–271

    PubMed  CAS  Google Scholar 

  8. Fujita N, Miyamoto T, Imai J, Hosogane N, Suzuki T, Yagi M, Morita K, Ninomiya K, Miyamoto K, Takaishi H, Matsumoto M, Morioka H, Yabe H, Chiba K, Watanabe S, Toyama Y, Suda T (2005) CD24 is expressed specifically in the nucleus pulposus of intervertebral discs. Biochem Biophys Res Commun 338:1890–1896

    Article  PubMed  CAS  Google Scholar 

  9. Ganey TM, Meisel HJ (2002) A potential role for cell-based therapeutics in the treatment of intervertebral disc herniation. Eur Spine J 11(Suppl 2):S206–S214

    PubMed  Google Scholar 

  10. Ganey T, Libera J, Moos V, Alasevic O, Fritsch KG, Meisel HJ, Hutton WC (2003) Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine 28:2609–2620

    Article  PubMed  Google Scholar 

  11. Gruber HE, Johnson TL, Leslie K, Ingram JA, Martin D, Hoelscher G, Banks D, Phieffer L, Coldham G, Hanley EN Jr (2002) Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat. Spine 27:1626–1633

    Article  PubMed  Google Scholar 

  12. Gorensek M, Jaksimović C, Kregar-Velikonja N, Gorensek M, Knezevic M, Jeras M, Pavlovcic V, Cör A (2004) Nucleus pulposus repair with cultured autologous elastic cartilage derived chondrocytes. Cell Mol Biol Lett 9:363–373

    PubMed  Google Scholar 

  13. 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 26:589–600

    Article  PubMed  CAS  Google Scholar 

  14. 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 [Epub ahead of print]

  15. Lee CR, Sakai D, Nakai T, Toyama K, Mochida J, Alini M, Grad S (2007) A phenotypic comparison of intervertebral disc and articular cartilage cells in the rat. Eur Spine J 16:2174–2185

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  17. 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 359:991–996

    Article  PubMed  CAS  Google Scholar 

  18. Maniadakis N (2000) Gray A (2000) The economic burden of back pain in the UK. Pain 84:95–103

    Article  PubMed  CAS  Google Scholar 

  19. Masuda K, Aota Y, Muehleman C, Imai Y, Okuma M, Thonar EJ, Andersson GB, An HS (2005) A novel rabbit model of mild, reproducible disc degeneration by an annulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine 30:5–14

    PubMed  Google Scholar 

  20. Meisel HJ, Ganey T, Hutton WC, Libera J, Minkus Y, Alasevic O (2006) Clinical experience in cell-based therapeutics: intervention and outcome. Eur Spine J 15:S397–S405

    Article  PubMed  Google Scholar 

  21. Mwale F, Roughley P, Antoniou J (2004) Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc. Eur Cell Mater 8:58–63

    PubMed  CAS  Google Scholar 

  22. Nishimura K, Mochida J (1998) Percutaneous reinsertion of the nucleus pulposus. An experimental study. Spine 23:1531–1538

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  24. Okuma M, Mochida J, Nishimura K, Sakabe K, Seiki K (2000) Reinsertion of stimulated nucleus pulposus cells retards intervertebral disc degeneration: an in vitro and in vivo experimental study. J Orthop Res 3:988–997

    Article  Google Scholar 

  25. Park JB, Chang H, Kim KW (2001) Expression of Fas ligand and apoptosis of disc cells in herniated lumbar disc tissue. Spine 26:618–621

    Article  PubMed  CAS  Google Scholar 

  26. Phillips FM, Reuben J, Wetzel FT (2002) Intervertebral disc degeneration adjacent to a lumbar fusion. An experimental rabbit model. J Bone Joint Surg Br 84:289–294

    Article  PubMed  CAS  Google Scholar 

  27. Risbud MV, Guttapalli A, Stokes DG, Hawkins D, Danielson KG, Schaer TP, Albert TJ, Shapiro IM (2006) Nucleus pulposus cells express HIF–1alpha under normoxic culture conditions: a metabolic adaptation to the intervertebral disc microenvironment. J Cell Biochem 98:152–159

    Article  PubMed  CAS  Google Scholar 

  28. 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 24:3531–3541

    Article  PubMed  CAS  Google Scholar 

  29. 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 regeneration7. Spine 30:2379–2387

    Article  PubMed  Google Scholar 

  30. 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 27:335–345

    Article  PubMed  CAS  Google Scholar 

  31. Semba K, Araki K, Li Z, Matsumoto K, Suzuki M, Nakagata N, Takagi K, Takeya M, Yoshinobu K, Araki M, Imai K, Abe K, Yamamura K (2006) A novel murine gene, Sickle tail, linked to the Danforth’s short tail locus, is required for normal development of the intervertebral disc. Genetics 172:445–456

    Article  PubMed  CAS  Google Scholar 

  32. Singh K, Masuda K, An HS (2005) Animal models for human disc degeneration. Spine J 5:267S–279S

    Article  PubMed  Google Scholar 

  33. Takada T, Nishida K, Doita M, Kurosaka M (2002) Fas ligand exists on intervertebral disc cells: a potential molecular mechanism for immune privilege of the disc. Spine 27:1526–1530

    Article  PubMed  Google Scholar 

  34. Thompson JP, Pearce RH, Schechter MT, Adams ME, Tsang IK, Bishop PB (1990) Preliminary evaluation of a scheme for grading the gross morphology of the human intervertebral disc. Spine 15:411–415

    Article  PubMed  CAS  Google Scholar 

  35. 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 co-culture system. Spine 29:1508–1514

    Article  PubMed  Google Scholar 

  36. 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 430:219–226

    Article  PubMed  Google Scholar 

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Acknowledgments

This work is supported by a grant from the Academic Frontier Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and a grant from AO Spine International.

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None of the authors has any potential conflict of interest.

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Correspondence to Daisuke Sakai.

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Sakai, D. Future perspectives of cell-based therapy for intervertebral disc disease. Eur Spine J 17 (Suppl 4), 452–458 (2008). https://doi.org/10.1007/s00586-008-0743-5

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  • DOI: https://doi.org/10.1007/s00586-008-0743-5

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