Advertisement

European Spine Journal

, Volume 17, Supplement 4, pp 492–503 | Cite as

Cell transplantation in lumbar spine disc degeneration disease

  • C. Hohaus
  • T. M. Ganey
  • Y. Minkus
  • H. J. Meisel
Review

Abstract

Low back pain is an extremely common symptom, affecting nearly three-quarters of the population sometime in their life. Given that disc herniation is thought to be an extension of progressive disc degeneration that attends the normal aging process, seeking an effective therapy that staves off disc degeneration has been considered a logical attempt to reduce back pain. The most apparent cellular and biochemical changes attributable to degeneration include a decrease in cell density in the disc that is accompanied by a reduction in synthesis of cartilage-specific extracellular matrix components. With this in mind, one therapeutic strategy would be to replace, regenerate, or augment the intervertebral disc cell population, with a goal of correcting matrix insufficiencies and restoring normal segment biomechanics. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. We designed an animal study using the dog as our model to investigate this hypothesis by transplantation of autologous disc-derived chondrocytes into degenerated intervertebral discs. As a result we demonstrated that disc cells remained viable after transplantation; transplanted disc cells produced an extracellular matrix that contained components similar to normal intervertebral disc tissue; a statistically significant correlation between transplanting cells and retention of disc height could displayed. Following these results the Euro Disc Randomized Trial was initiated to embrace a representative patient group with persistent symptoms that had not responded to conservative treatment where an indication for surgical treatment was given. In the interim analyses we evaluated that patients who received autologous disc cell transplantation had greater pain reduction at 2 years compared with patients who did not receive cells following their discectomy surgery and discs in patients that received cells demonstrated a significant difference as a group in the fluid content of their treated disc when compared to control. Autologous disc-derived cell transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration. Adipose tissue provides an alternative source of regenerative cells with little donor site morbidity. These regenerative cells are able to differentiate into a nucleus pulposus-like phenotype when exposed to environmental factors similar to disc, and offer the inherent advantage of availability without the need for transporting, culturing, and expanding the cells. In an effort to develop a clinical option for cell placement and assess the response of the cells to the post-surgical milieu, adipose-derived cells were collected, concentrated, and transplanted under fluoroscopic guidance directly into a surgically damaged disc using our dog model. This study provides evidence that cells harvested from adipose tissue might offer a reliable source of regenerative potential capable of bio-restitution.

Keywords

Autologous disc cell transplantation Adipose-derived stem cells Degenerative disc disease Cell transplantation Biological repair 

Notes

Conflict of interest statement

None of the authors has any potential conflict of interest.

References

  1. 1.
    Annunen S, Paassilta P, Lohiniva J, Perala M, Pihlajamaa T, Karppinen J, Tervonen O, Kroger H, Lahde S, Vanharanta H, Ryhanen L, Goring HH, Ott J, Prockop DJ, Ala-Kokko L (1999) An allele of COL9A2 associated with intervertebral disc disease. Science 285:409–412PubMedCrossRefGoogle Scholar
  2. 2.
    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 98:996–1003PubMedCrossRefGoogle Scholar
  3. 3.
    Beard HK, Roberts S, O’Brien JP (1981) Immunofluorescent staining for collagen and proteoglycan in normal and scoliotic intervertebral discs. J Bone Joint Surg Br 63B:529–534PubMedGoogle Scholar
  4. 4.
    Beard HK, Ryvar R, Brown R, Muir H (1980) Immunochemical localization of collagen types and proteoglycan in pig intervertebral discs. Immunology 41:491–501PubMedGoogle Scholar
  5. 5.
    Bibby SR, Jones DA, Lee RB, Yu J, Urban JPG (2001) The pathophysiology of the intervertebral disc. Joint Bone Spine 68:537–542PubMedCrossRefGoogle Scholar
  6. 6.
    Boden SD, McCowin PR, Davis DO, Dina TS, Mark AS, Wiesel S (1990) Abnormal magnetic-resonance scans of the cervical spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg Am 72:1178–1184PubMedGoogle Scholar
  7. 7.
    Buckwalter JA (1995) Aging and degeneration of the human intervertebral disc. Spine 20:1307–1314PubMedGoogle Scholar
  8. 8.
    Doers TM, Kang JD (1999) The biomechanics and biochemistry of disc degeneration. Curr Opin in Orthop 10:117–121CrossRefGoogle Scholar
  9. 9.
    Eyre DR (1988) Collagens of the disc. In: Ghosh P (ed) The biology of the intervertebral disc. CRC Press, Boca Raton, pp 171–188Google Scholar
  10. 10.
    Flynn JC, Hoque MA (1979) Anterior fusion of the lumbar spine. End-result study with long-term follow-up. J Bone Joint Surg Am 61:1143–1150PubMedGoogle Scholar
  11. 11.
    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 28:2609–2620PubMedCrossRefGoogle Scholar
  12. 12.
    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–S214PubMedGoogle Scholar
  13. 13.
    Gruber HE, Hanley EN Jr (1998) Analysis of aging and degeneration of the human intervertebral disc. Comparison of surgical specimens with normal controls. Spine 23:751–757PubMedCrossRefGoogle Scholar
  14. 14.
    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 27:1626–1633PubMedCrossRefGoogle Scholar
  15. 15.
    Katz AJ, Llull R, Hedrick MH, Futrell JW (1999) Emerging approaches to the tissue engineering of fat. Clin Plast Surg 26:587–603 viiiPubMedGoogle Scholar
  16. 16.
    Kawaguchi Y, Osada R, Kanamori M, Ishihara H, Ohmori K, Matsui H, Kimura T (1999) Association between an aggrecan gene polymorphism and lumbar disc degeneration. Spine 24:2456–2460PubMedCrossRefGoogle Scholar
  17. 17.
    Lauerman WC, Bradford DS, Ogilvie JW, Transfeldt EE (1992) Results of lumbar pseudarthrosis repair. J Spinal Disord 5:149–157PubMedCrossRefGoogle Scholar
  18. 18.
    Malko JA, Hutton WC, Fajman WA (2002) An in vivo MRI study of the changes in volume (and fluid content) of the lumbar intervertebral disc after overnight bed rest and during an 8-hour walking protocol. J Spinal Disord Tech 15:157–163PubMedGoogle Scholar
  19. 19.
    Maroudas A, Stockwell RA, Nachemson A, Urban J (1975) Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. J Anat 120:113–130PubMedGoogle Scholar
  20. 20.
    Nerlich AG, Schleicher ED, Boos N (1997) 1997 Volvo Award winner in basic science studies. Immunohistologic markers for age-related changes of human lumbar intervertebral discs. Spine 22:2781–2795PubMedCrossRefGoogle Scholar
  21. 21.
    Norwig J, Josimovic-Alasevic O, Fritsch KG, Steinof K, Siodla W (2000) Integrated isolator technology-based sterile production of cell-based drugs. Pharm Ind 63:780–784Google Scholar
  22. 22.
    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 18:988–997PubMedCrossRefGoogle Scholar
  23. 23.
    Osti OL, Vernon-Roberts B, Fraser RD (1990) 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model. Spine 15:762–767PubMedCrossRefGoogle Scholar
  24. 24.
    Paassilta P, Lohiniva J, Goring HH, Perala M, Raina SS, Karppinen J (2000) Identification of a common risc factor for lumbar disk disease. JAMA 285:1843–1849CrossRefGoogle Scholar
  25. 25.
    Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N (2001) Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine 26:1873–1878PubMedCrossRefGoogle Scholar
  26. 26.
    Prolo DJ, Oklund SA, Butcher M (1986) Toward uniformity in evaluating results of lumbar spine operations. A paradigm applied to posterior lumbar interbody fusions. Spine 11:601–606PubMedCrossRefGoogle Scholar
  27. 27.
    Roberts S, McCall IW, Menage J, Haddaway MJ, Eisenstein SM (1997) Does the thickness of the vertebral subchondral bone reflect the composition of the intervertebral disc? Eur Spine J 6:385–389PubMedCrossRefGoogle Scholar
  28. 28.
    Roberts S, Menage J, Duance V, Wotton SF (1991) Type III collagen in the intervertebral disc. Histochem J 23:503–508PubMedCrossRefGoogle Scholar
  29. 29.
    Steinmann JC, Herkowitz HN (1992) Pseudarthrosis of the spine. Clin Orthop Relat Res 284:80–90Google Scholar
  30. 30.
    Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, Fraser JK, Hedrick MH (2005) Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med 54:132–141PubMedCrossRefGoogle Scholar
  31. 31.
    Sun Y, Hurtig M, Pilliar RM, Grynpas M, Kandel RA (2001) Characterization of nucleus pulposus-like tissue formed in vitro. J Orthop Res 19:1078–1084PubMedCrossRefGoogle Scholar
  32. 32.
    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 15:411–415PubMedCrossRefGoogle Scholar
  33. 33.
    Videman T, Leppavuori J, Kaprio J, Battie MC, Gibbons LE, Peltonen L, Koskenvuo M (1998) Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration. Spine 23:2477–2485PubMedCrossRefGoogle Scholar
  34. 34.
    Waddell G, Kummel EG, Lotto WN, Graham JD, Hall H, McCulloch JA (1979) Failed lumbar disc surgery and repeat surgery following industrial injuries. J Bone Joint Surg Am 61:201–207PubMedGoogle Scholar
  35. 35.
    West JL 3rd, Bradford DS, Ogilvie JW (1991) Results of spinal arthrodesis with pedicle screw-plate fixation. J Bone Joint Surg Am 73:1179–1184PubMedGoogle Scholar
  36. 36.
    Wu JJ, Eyre DR, Slayter HS (1987) Type VI collagen of the intervertebral disc. Biochemical and electron-microscopic characterization of the native protein. Biochem J 248:373–381PubMedGoogle Scholar
  37. 37.
    Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • C. Hohaus
    • 1
    • 2
  • T. M. Ganey
    • 3
  • Y. Minkus
    • 1
  • H. J. Meisel
    • 1
    • 2
  1. 1.Department of NeurosurgeryBG-Clinic BergmannstrostHalleGermany
  2. 2.Translational Center of Regenerative MedicineUniversity of LeipzigLeipzigGermany
  3. 3.Atlanta Medical CenterAtlantaUSA

Personalised recommendations