Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2016, Article ID 5952165, 14 pages
http://dx.doi.org/10.1155/2016/5952165
Review Article

A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic

1The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia
2Department of Neurosurgery, Monash Medical Centre, Clayton, VIC 3168, Australia
3Department of Surgery, Monash University, Clayton, VIC 3168, Australia
4Proteobioactives, Pty. Ltd., Balgowlah, NSW 2093, Australia
5Department of Neurosurgery, St Vincent’s Private Hospital, Fitzroy, VIC 3065, Australia

Received 18 March 2016; Accepted 3 May 2016

Academic Editor: Oreste Gualillo

Copyright © 2016 Chris Daly 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. D. Hoy, L. March, P. Brooks et al., “The global burden of low back pain: estimates from the Global Burden of Disease 2010 study,” Annals of the Rheumatic Diseases, vol. 73, no. 6, pp. 968–974, 2014. View at Publisher · View at Google Scholar · View at Scopus
  2. K. Luoma, H. Riihimäki, R. Luukkonen, R. Raininko, E. Viikari-Juntura, and A. Lamminen, “Low back pain in relation to lumbar disc degeneration,” Spine, vol. 25, no. 4, pp. 487–492, 2000. View at Publisher · View at Google Scholar · View at Scopus
  3. M. D. Humzah and R. W. Soames, “Human intervertebral disc: structure and function,” Anatomical Record, vol. 220, no. 4, pp. 337–356, 1988. View at Publisher · View at Google Scholar · View at Scopus
  4. F. Marchand and A. M. Ahmed, “Investigation of the laminate structure of lumbar disc anulus fibrosus,” Spine, vol. 15, no. 5, pp. 402–410, 1990. View at Publisher · View at Google Scholar · View at Scopus
  5. P. Colombier, J. Clouet, O. Hamel, L. Lescaudron, and J. Guicheux, “The lumbar intervertebral disc: from embryonic development to degeneration,” Joint Bone Spine, vol. 81, no. 2, pp. 125–129, 2014. View at Publisher · View at Google Scholar · View at Scopus
  6. A. J. Freemont, “The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain,” Rheumatology, vol. 48, no. 1, pp. 5–10, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. M. A. Adams and P. J. Roughley, “What is intervertebral disc degeneration, and what causes it?” Spine, vol. 31, no. 18, pp. 2151–2161, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. L. A. Setton and J. Chen, “Mechanobiology of the intervertebral disc and relevance to disc degeneration,” The Journal of Bone & Joint Surgery—American Volume, vol. 88, supplement 2, pp. 52–57, 2006. View at Google Scholar
  9. W. Johannessen, E. J. Vresilovic, A. C. Wright, and D. M. Elliott, “Intervertebral disc mechanics are restored following cyclic loading and unloaded recovery,” Annals of Biomedical Engineering, vol. 32, no. 1, pp. 70–76, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. S. R. Pye, D. M. Reid, J. E. Adams, A. J. Silman, and T. W. O'Neill, “Influence of weight, body mass index and lifestyle factors on radiographic features of lumbar disc degeneration,” Annals of the Rheumatic Diseases, vol. 66, no. 3, pp. 426–427, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. C. L. Le Maitre, A. J. Freemont, and J. A. Hoyland, “Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration,” Arthritis Research and Therapy, vol. 9, no. 3, article R45, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. J. P. G. Urban and S. Roberts, “Degeneration of the intervertebral disc,” Arthritis Research and Therapy, vol. 5, no. 3, pp. 120–130, 2003. View at Google Scholar · View at Scopus
  13. C. L. Le Maitre, A. Pockert, D. J. Buttle, A. J. Freemont, and J. A. Hoyland, “Matrix synthesis and degradation in human intervertebral disc degeneration,” Biochemical Society Transactions, vol. 35, part 4, pp. 652–655, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. R. J. Moore, B. Vernon-Roberts, R. D. Fraser, O. L. Osti, and M. Schembri, “The origin and fate of herniated lumbar intervertebral disc tissue,” Spine, vol. 21, no. 18, pp. 2149–2155, 1996. View at Publisher · View at Google Scholar · View at Scopus
  15. B. Peng, W. Wu, S. Hou, P. Li, C. Zhang, and Y. Yang, “The pathogenesis of discogenic low back pain,” The Journal of Bone & Joint Surgery—British Volume, vol. 87, no. 1, pp. 62–67, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. C. Liang, H. Li, Y. Tao et al., “New hypothesis of chronic back pain: low pH promotes nerve ingrowth into damaged intervertebral disks,” Acta Anaesthesiologica Scandinavica, vol. 57, no. 3, pp. 271–277, 2013. View at Publisher · View at Google Scholar · View at Scopus
  17. P.-P. A. Vergroesen, I. Kingma, K. S. Emanuel et al., “Mechanics and biology in intervertebral disc degeneration: a vicious circle,” Osteoarthritis and Cartilage, vol. 23, no. 7, pp. 1057–1070, 2015. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Sahlman, R. Inkinen, T. Hirvonen et al., “Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for type II collagen,” Spine, vol. 26, no. 23, pp. 2558–2565, 2001. View at Publisher · View at Google Scholar · View at Scopus
  19. J. H. Jeong, J. H. Lee, E. S. Jin, J. K. Min, S. R. Jeon, and K. H. Choi, “Regeneration of intervertebral discs in a rat disc degeneration model by implanted adipose-tissue-derived stromal cells,” Acta Neurochirurgica, vol. 152, no. 10, pp. 1771–1777, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. K. Masuda, Y. Aota, C. Muehleman et al., “A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: Correlation between the degree of disc injury and radiological and histological appearances of disc degeneration,” Spine, vol. 30, no. 1, pp. 5–14, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. N. Bergknut, J. P. H. J. Rutges, H.-J. C. Kranenburg et al., “The dog as an animal model for intervertebral disc degeneration?” Spine, vol. 37, no. 5, pp. 351–358, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. Y. Zhang, S. Drapeau, H. S. An, D. Markova, B. A. Lenart, and D. G. Anderson, “Histological features of the degenerating intervertebral disc in a goat disc-injury model,” Spine, vol. 36, no. 19, pp. 1519–1527, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. D. Oehme, P. Ghosh, S. Shimmon et al., “Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model,” Journal of Neurosurgery Spine, vol. 20, no. 6, pp. 657–669, 2014. View at Publisher · View at Google Scholar
  24. W. C. Lauerman, R. C. Platenberg, J. E. Cain, and V. F. X. Deeney, “Age-related disk degeneration: preliminary report of a naturally occurring baboon model,” Journal of Spinal Disorders, vol. 5, no. 2, pp. 170–174, 1992. View at Publisher · View at Google Scholar · View at Scopus
  25. R. C. Platenberg, G. B. Hubbard, W. J. Ehler, and C. J. Hixson, “Spontaneous disc degeneration in the baboon model: magnetic resonance imaging and histopathologic correlation,” Journal of Medical Primatology, vol. 30, no. 5, pp. 268–272, 2001. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Alini, S. M. Eisenstein, K. Ito et al., “Are animal models useful for studying human disc disorders/degeneration?” European Spine Journal, vol. 17, no. 1, pp. 2–19, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. D. J. Aguiar, S. L. Johnson, and T. R. Oegema Jr., “Notochordal cells interact with nucleus pulposus cells: Regulation of proteoglycan synthesis,” Experimental Cell Research, vol. 246, no. 1, pp. 129–137, 1999. View at Publisher · View at Google Scholar · View at Scopus
  28. T. R. Oegema, S. L. Johnson, D. J. Aguiar, and J. W. Ogilvie, “Fibronectin and its fragments increase with degeneration in the human intervertebral disc,” Spine, vol. 25, no. 21, pp. 2742–2747, 2000. View at Publisher · View at Google Scholar · View at Scopus
  29. J. W. Stevens, G. L. Kurriger, A. S. Carter, and J. A. Maynard, “CD44 expression in the developing and growing rat intervertebral disc,” Developmental Dynamics, vol. 219, no. 3, pp. 381–390, 2000. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Sobajima, J. F. Kompel, J. S. Kim et al., “A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology,” Spine, vol. 30, no. 1, pp. 15–24, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. J. C. Lotz and J. R. Chin, “Intervertebral disc cell death is dependent on the magnitude and duration of spinal loading,” Spine, vol. 25, no. 12, pp. 1477–1483, 2000. View at Publisher · View at Google Scholar · View at Scopus
  32. T. Yurube, H. Hirata, K. Kakutani et al., “Notochordal cell disappearance and modes of apoptotic cell death in a rat tail static compression-induced disc degeneration model,” Arthritis Research and Therapy, vol. 16, article R31, 2014. View at Publisher · View at Google Scholar · View at Scopus
  33. H. E. Gruber and E. N. Hanley, “Analysis of aging and degeneration of the human intervertebral disc. Comparison of surgical specimens with normal controls,” Spine, vol. 23, no. 7, pp. 751–757, 1998. View at Publisher · View at Google Scholar · View at Scopus
  34. G. D. O'Connell, E. J. Vresilovic, and D. M. Elliott, “Comparison of animals used in disc research to human lumbar disc geometry,” Spine, vol. 32, no. 3, pp. 328–333, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. K. D. K. Luk, D. K. Ruan, D. H. K. Chow, and J. C. Y. Leong, “Intervertebral disc autografting in a bipedal animal model,” Clinical Orthopaedics and Related Research, no. 337, pp. 13–26, 1997. View at Google Scholar · View at Scopus
  36. C. W. Goff and W. Landmesser, “Bipedal rats and mice,” The Journal of Bone & Joint Surgery—American Volume, vol. 39, no. 3, pp. 616–622, 1957. View at Google Scholar
  37. H.-J. Wilke, A. Rohlmann, S. Neller, F. Graichen, L. Claes, and G. Bergmannt, “ISSLS prize winner: a novel approach to determine trunk muscle forces during flexion and extension: a comparison of data from an in vitro experiment and in vivo measurements,” Spine, vol. 28, no. 23, pp. 2585–2593, 2003. View at Publisher · View at Google Scholar · View at Scopus
  38. T. Kimura, K. Nakata, N. Tsumaki et al., “Progressive degeneration of articular cartilage and intervertebral discs: an experimental study in transgenic mice bearing a type IX collagen mutation,” International Orthopaedics, vol. 20, no. 3, pp. 177–181, 1996. View at Publisher · View at Google Scholar · View at Scopus
  39. C. Court, O. K. Colliou, J. R. Chin, E. Liebenberg, D. S. Bradford, and J. C. Lotz, “The effect of static in vivo bending on the murine intervertebral disc,” Spine Journal, vol. 1, no. 4, pp. 239–245, 2001. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Higuchi, K. abe, and K. Kaneda, “Changes in the nucleus pulposus of the intervertebral disc in bipedal mice: a light and electron microscopic study,” Clinical Orthopaedics and Related Research, vol. 175, article 251, 1983. View at Google Scholar
  41. S. Miyamoto, K. Yonenobu, and K. Ono, “Experimental cervical spondylosis in the mouse,” Spine, vol. 16, pp. S495–S500, 1991. View at Publisher · View at Google Scholar · View at Scopus
  42. R. E. Hammer, S. D. Maika, J. A. Richardson, J.-P. Tang, and J. D. Taurog, “Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β2m: an animal model of HLA-B27-associated human disorders,” Cell, vol. 63, no. 5, pp. 1099–1112, 1990. View at Publisher · View at Google Scholar · View at Scopus
  43. K. Lindblom, “Intervertebral-disc degeneration considered as a pressure atrophy,” The Journal of Bone and Joint Surgery. American, vol. 39, no. 4, pp. 933–945, 1957. View at Google Scholar
  44. J. C. Iatridis, P. L. Mente, I. A. F. Stokes, D. D. Aronsson, and M. Alini, “Compression-induced changes in intervertebral disc properties in a rat tail model,” Spine, vol. 24, no. 10, pp. 996–1002, 1999. View at Publisher · View at Google Scholar · View at Scopus
  45. C. T. S. Ching, D. H. K. Chow, F. Y. D. Yao, and A. D. Holmes, “The effect of cyclic compression on the mechanical properties of the inter-vertebral disc: an in vivo study in a rat tail model,” Clinical Biomechanics, vol. 18, no. 3, pp. 182–189, 2003. View at Publisher · View at Google Scholar · View at Scopus
  46. M.-A. A. Rousseau, J. A. Ulrich, E. C. Bass, A. G. Rodriguez, J. J. Liu, and J. C. Lotz, “Stab incision for inducing intervertebral disc degeneration in the rat,” Spine, vol. 32, no. 1, pp. 17–24, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. J. H. Jeong, E. S. Jin, J. K. Min et al., “Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat,” Cytotechnology, vol. 59, no. 1, pp. 55–64, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. R. Silberberg, M. Aufdermaur, and J. H. Adler, “Degeneration of the intervertebral disks and spondylosis in aging sand rats,” Archives of Pathology and Laboratory Medicine, vol. 103, no. 5, pp. 231–235, 1979. View at Google Scholar · View at Scopus
  49. H. E. Gruber, T. Johnson, H. J. Norton, and E. N. Hanley Jr., “The sand rat model for disc degeneration: radiologic characterization of age-related changes: cross-sectional and prospective analyses,” Spine, vol. 27, no. 3, pp. 230–234, 2002. View at Publisher · View at Google Scholar · View at Scopus
  50. R. W. Moskowitz, I. Ziv, C. W. Denko, B. Boja, P. K. Jones, and J. H. Adler, “Spondylosis in sand rats: a model of intervertebral disc degeneration and hyperostosis,” Journal of Orthopaedic Research, vol. 8, no. 3, pp. 401–411, 1990. View at Publisher · View at Google Scholar · View at Scopus
  51. M. W. Kroeber, F. Unglaub, H. Wang et al., “New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration,” Spine, vol. 27, no. 23, pp. 2684–2690, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. F. M. Phillips, J. Reuben, and F. T. Wetzel, “Intervertebral disc degeneration adjacent to a lumbar fusion,” Journal of Bone and Joint Surgery B, vol. 84, no. 2, pp. 289–294, 2002. View at Publisher · View at Google Scholar · View at Scopus
  53. D. P. Kiester, J. M. Williams, G. B. J. Andersson, E. J. M. A. Thonar, and T. W. McNeill, “The dose-related effect of intradiscal chymopapain on rabbit intervertebral discs,” Spine, vol. 19, no. 7, pp. 747–751, 1994. View at Publisher · View at Google Scholar · View at Scopus
  54. D. Sakai, J. Mochida, T. Iwashina 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, vol. 30, no. 21, pp. 2379–2387, 2005. View at Publisher · View at Google Scholar · View at Scopus
  55. D. C. Keyes and E. L. Compere, “The normal and pathological physiology of the nucleus pulposus of the intervertebral disc,” The Journal of Bone & Joint Surgery—American Volume, vol. 14, no. 4, pp. 897–938, 1932. View at Google Scholar
  56. C. Hohaus, T. M. Ganey, Y. Minkus, and H. J. Meisel, “Cell transplantation in lumbar spine disc degeneration disease,” European Spine Journal, vol. 17, supplement 4, pp. 492–503, 2008. View at Publisher · View at Google Scholar
  57. N. A. Gillett, R. Gerlach, J. J. Cassidy, and S. A. Brown, “Age-related changes in the beagle spine,” Acta Orthopaedica, vol. 59, no. 5, pp. 503–507, 1988. View at Publisher · View at Google Scholar · View at Scopus
  58. K. Serigano, D. Sakai, A. Hiyama, F. Tamura, M. Tanaka, and J. Mochida, “Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model,” Journal of Orthopaedic Research, vol. 28, no. 10, pp. 1267–1275, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. J. Melrose, T. K. F. Taylor, P. Ghosh, C. Holbert, C. Macpherson, and C. R. Bellenger, “Intervertebral disc reconstitution after chemonucleolysis with chymopapain is dependent on dosage: an experimental study in beagle dogs,” Spine, vol. 21, no. 1, pp. 9–17, 1996. View at Publisher · View at Google Scholar · View at Scopus
  60. R. J. W. Hoogendoorn, M. N. Helder, R. J. Kroeze, R. A. Bank, T. H. Smit, and P. I. J. M. Wuisman, “Reproducible long-term disc degeneration in a large animal model,” Spine, vol. 33, no. 9, pp. 949–954, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. F. L. Acosta Jr., L. Metz, H. D. Adkisson et al., “Porcine intervertebral disc repair using allogeneic juvenile articular chondrocytes or mesenchymal stem cells,” Tissue Engineering—Part A, vol. 17, no. 23-24, pp. 3045–3055, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. O. L. Osti, B. Vernon-Roberts, and R. D. Fraser, “Anulus tears and intervertebral disc degeneration: an experimental study using an animal model,” Spine, vol. 15, no. 8, pp. 762–767, 1990. View at Google Scholar · View at Scopus
  63. D. Oehme, T. Goldschlager, S. Shimon, and J. Wu, “Radiological, morphological, histological and biochemical changes of lumbar discs in an animal model of disc degeneration suitable for evaluating the potential regenerative capacity of novel biological agents,” Journal of Tissue Science & Engineering, vol. 6, article 153, 2015. View at Publisher · View at Google Scholar
  64. J. Melrose, C. Shu, C. Young et al., “Mechanical destabilization induced by controlled annular incision of the intervertebral disc dysregulates metalloproteinase expression and induces disc degeneration,” Spine, vol. 37, no. 1, pp. 18–25, 2012. View at Publisher · View at Google Scholar · View at Scopus
  65. P. Ghosh, R. Moore, B. Vernon-Roberts et al., “Immunoselected STRO-3+ mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs: laboratory investigation,” Journal of Neurosurgery: Spine, vol. 16, no. 5, pp. 479–488, 2012. View at Publisher · View at Google Scholar · View at Scopus
  66. D. J. Nuckley, P. A. Kramer, A. Del Rosario, N. Fabro, S. Baran, and R. P. Ching, “Intervertebral disc degeneration in a naturally occurring primate model: radiographic and biomechanical evidence,” Journal of Orthopaedic Research, vol. 26, no. 9, pp. 1283–1288, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. W. E. Stern and W. F. Coulson, “Effects of collagenase upon the intervertebral disc in monkeys,” Journal of Neurosurgery, vol. 44, no. 1, pp. 32–44, 1976. View at Publisher · View at Google Scholar · View at Scopus
  68. F. Wei, R. Zhong, Z. Zhou et al., “In vivo experimental intervertebral disc degeneration induced by bleomycin in the rhesus monkey,” BMC Musculoskeletal Disorders, vol. 15, article 340, 2014. View at Publisher · View at Google Scholar · View at Scopus
  69. A. S. Bailey, F. Adler, S. Min Lai, and M. A. Asher, “A comparison between bipedal and quadrupedal rats: do bipedal rats actually assume an upright posture?” Spine, vol. 26, no. 14, pp. E308–E313, 2001. View at Publisher · View at Google Scholar · View at Scopus
  70. J. P. Norcross, G. E. Lester, P. Weinhold, and L. E. Dahners, “An in vivo model of degenerative disc disease,” Journal of Orthopaedic Research, vol. 21, no. 1, pp. 183–188, 2003. View at Publisher · View at Google Scholar · View at Scopus
  71. T. Miyamoto, T. Muneta, T. Tabuchi et al., “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 Research and Therapy, vol. 12, no. 6, article R206, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. H.-J. Wilke, A. Kettler, K. H. Wenger, and L. E. Claes, “Anatomy of the sheep spine and its comparison to the human spine,” Anatomical Record, vol. 247, no. 4, pp. 542–555, 1997. View at Publisher · View at Google Scholar · View at Scopus
  73. T. H. Smit, “The use of a quadruped as an in vivo model for the study of the spine—biomechanical considerations,” European Spine Journal, vol. 11, no. 2, pp. 137–144, 2002. View at Publisher · View at Google Scholar · View at Scopus
  74. R. J. W. Hoogendoorn, M. N. Helder, T. H. Smit, and P. I. J. M. Wuisman, “Notochordal cells in mature caprine intervertebral discs,” European Cells and Materials, vol. 10, no. 3, p. 59, 2005. View at Google Scholar · View at Scopus
  75. C. J. Hunter, J. R. Matyas, and N. A. Duncan, “Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison,” Journal of Anatomy, vol. 205, no. 5, pp. 357–362, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. H. J. Wilke, A. Kettler, and L. E. Claes, “Are sheep spines a valid biomechanical model for human spines?” Spine, vol. 22, no. 20, pp. 2365–2374, 1997. View at Publisher · View at Google Scholar
  77. T. Goldschlager, J. V. Rosenfeld, P. Ghosh et al., “Cervical interbody fusion is enhanced by allogeneic mesenchymal precursor cells in an ovine model,” Spine, vol. 36, no. 8, pp. 615–623, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. T. Goldschlager, P. Ghosh, A. Zannettino et al., “A comparison of mesenchymal precursor cells and amnion epithelial cells for enhancing cervical interbody fusion in an ovine model,” Neurosurgery, vol. 68, no. 4, pp. 1025–1035, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. T. Goldschlager, P. Ghosh, A. Zannettino et al., “Cervical motion preservation using mesenchymal progenitor cells and pentosan polysulfate, a novel chondrogenic agent: preliminary study in an ovine model,” Neurosurgical Focus, vol. 28, no. 6, article E4, 2010. View at Google Scholar
  80. G. W. Omlor, A. G. Nerlich, H.-J. Wilke et al., “A new porcine in vivo animal model of disc degeneration: response of anulus fibrosus cells, chondrocyte-like nucleus pulposus cells, and notochordal nucleus pulposus cells to partial nucleotomy,” Spine, vol. 34, no. 25, pp. 2730–2739, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. P. Ghosh, R. Moore, B. Vernon-Roberts et al., “Immunoselected STRO-3+ mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs,” Journal of Neurosurgery: Spine, vol. 16, no. 5, pp. 479–488, 2012. View at Publisher · View at Google Scholar
  82. D. Sakai, J. Mochida, T. Iwashina et al., “Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc,” Biomaterials, vol. 27, no. 3, pp. 335–345, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. J. C. Lotz, “Animal models of intervertebral disc degeneration: lessons learned,” Spine, vol. 29, no. 23, pp. 2742–2750, 2004. View at Publisher · View at Google Scholar · View at Scopus
  84. K. Singh, K. Masuda, and H. S. An, “Animal models for human disc degeneration,” The Spine Journal, vol. 5, no. 6, 2005. View at Publisher · View at Google Scholar · View at Scopus
  85. R. Silberberg, “Histologic and morphometric observations on vertebral bone of aging sand rats,” Spine, vol. 13, no. 2, pp. 202–208, 1988. View at Publisher · View at Google Scholar · View at Scopus
  86. H. E. Gruber, T. L. Johnson, K. Leslie et al., “Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat,” Spine, vol. 27, no. 15, pp. 1626–1633, 2002. View at Publisher · View at Google Scholar · View at Scopus
  87. C. W. A. Pfirrmann, A. Metzdorf, M. Zanetti, J. Hodler, and N. Boos, “Magnetic resonance classification of lumbar intervertebral disc degeneration,” Spine, vol. 26, no. 17, pp. 1873–1878, 2001. View at Publisher · View at Google Scholar · View at Scopus
  88. N. Bergknut, E. Auriemma, S. Wijsman et al., “Evaluation of intervertebral disk degeneration in chondrodystrophic and nonchondrodystrophic dogs by use of Pfirrmann grading of images obtained with low-field magnetic resonance imaging,” American Journal of Veterinary Research, vol. 72, no. 7, pp. 893–898, 2011. View at Publisher · View at Google Scholar · View at Scopus
  89. J. L. Kelsey, P. B. Githens, T. O’Conner et al., “Acute prolapsed lumbar intervertebral disc. An epidemiologic study with special reference to driving automobiles and cigarette smoking,” Spine, vol. 9, no. 6, pp. 608–613, 1984. View at Publisher · View at Google Scholar · View at Scopus
  90. K. Yamada, “The dynamics of experimental posture. Experimental study of intervertebral disk herniation in bipedal animals,” Clinical Orthopaedics, vol. 25, pp. 20–31, 1962. View at Google Scholar
  91. C. K. Lee and N. A. Langrana, “Lumbosacral spinal fusion a biomechanical study,” Spine, vol. 9, no. 6, pp. 574–581, 1984. View at Publisher · View at Google Scholar · View at Scopus
  92. R. C. Quinnell and H. R. Stockdale, “Some experimental observations of the influence of a single lumbar floating fusion on the remaining lumbar spine,” Spine, vol. 6, no. 3, pp. 263–267, 1981. View at Publisher · View at Google Scholar · View at Scopus
  93. L. Smith, “Enzyme dissolution of the nucleus pulposus in humans,” The Journal of the American Medical Association, vol. 187, no. 2, pp. 137–140, 1964. View at Publisher · View at Google Scholar
  94. L. Smith and J. E. Brown, “Treatment of lumbar intervertebral disc lesions by direct injection of chymopapain,” The Journal of Bone & Joint Surgery—British Volume, vol. 49, no. 3, pp. 502–519, 1967. View at Google Scholar · View at Scopus
  95. D. S. Bradford, T. R. Oegema Jr., K. M. Cooper, K. Wakano, and E. Y. Chao, “Chymopapain, chemonucleolysis, and nucleus pulposus regeneration. A biochemical and biomechanical study,” Spine, vol. 9, no. 2, pp. 135–147, 1984. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Sakuma, N. Fujii, T. Takahashi, J. Hoshino, S. Miyauchi, and H. Iwata, “Effect of chondroitinase ABC on matrix metalloproteinases and inflammatory mediators produced by intervertebral disc of rabbit in vitro,” Spine, vol. 27, no. 6, pp. 576–580, 2002. View at Publisher · View at Google Scholar · View at Scopus
  97. NC-IUBMB, Enzyme Nomenclature 1992: Recommendations of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology on the Nomenclature and Classification of Enzymes, Academic Press, San Diego, Calif, USA, 1992.
  98. R. J. Hoogendoorn, P. I. Wuisman, T. H. Smit, V. E. Everts, and M. N. Helder, “Experimental intervertebral disc degeneration induced by chondroitinase ABC in the goat,” Spine, vol. 32, no. 17, pp. 1816–1825, 2007. View at Publisher · View at Google Scholar · View at Scopus
  99. D. Oehme, P. Ghosh, T. Goldschlager et al., “Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate,” Journal of Neurosurgery: Spine, vol. 24, no. 5, pp. 715–726, 2016. View at Publisher · View at Google Scholar
  100. S. Holm, A. K. Holm, L. Ekström, A. Karladani, and T. Hansson, “Experimental disc degeneration due to endplate injury,” Journal of Spinal Disorders and Techniques, vol. 17, no. 1, pp. 64–71, 2004. View at Publisher · View at Google Scholar · View at Scopus
  101. G. Cinotti, C. D. Rocca, S. Romeo, F. Vittur, R. Toffanin, and G. Trasimeni, “Degenerative changes of porcine intervertebral disc induced by vertebral endplate injuries,” Spine, vol. 30, no. 2, pp. 174–180, 2005. View at Publisher · View at Google Scholar · View at Scopus
  102. D. Oehme, T. Goldschlager, J. Rosenfeld et al., “Lateral surgical approach to lumbar intervertebral discs in an ovine model,” ScientificWorldJournal, vol. 2012, Article ID 873726, 8 pages, 2012. View at Publisher · View at Google Scholar
  103. D. Oehme, T. Goldschlager, P. Ghosh, J. V. Rosenfeld, and G. Jenkin, “Cell-based therapies used to treat lumbar degenerative disc disease: a systematic review of animal studies and human clinical trials,” Stem Cells International, vol. 2015, no. 2, pp. 946031–946016, 2015. View at Publisher · View at Google Scholar · View at Scopus
  104. K. D. K. Luk, D. K. Ruan, D. S. Lu, and Z. Q. Fei, “Fresh frozen intervertebral disc allografting in a bipedal animal model,” Spine, vol. 28, no. 9, pp. 864–870, 2003. View at Publisher · View at Google Scholar · View at Scopus
  105. H. J. Meisel, V. Siodla, T. Ganey, Y. Minkus, W. C. Hutton, and O. J. Alasevic, “Clinical experience in cell-based therapeutics: disc chondrocyte transplantation: a treatment for degenerated or damaged intervertebral disc,” Biomolecular Engineering, vol. 24, no. 1, pp. 5–21, 2007. View at Publisher · View at Google Scholar
  106. L. Orozco, R. Soler, C. Morera, M. Alberca, A. Sánchez, and J. García-Sancho, “Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study,” Transplantation, vol. 92, no. 7, pp. 822–828, 2011. View at Publisher · View at Google Scholar · View at Scopus
  107. T. Yoshikawa, Y. Ueda, K. Miyazaki, M. Koizumi, and Y. Takakura, “Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies,” Spine, vol. 35, no. 11, pp. E475–E480, 2010. View at Publisher · View at Google Scholar · View at Scopus
  108. H. W. Bae, K. Amirdelfan, D. Coric et al., “A phase II study demonstrating efficacy and safety of mesenchymal precursor cells in low back pain due to disc degeneration,” The Spine Journal, vol. 14, no. 11, pp. S31–S32, 2014. View at Publisher · View at Google Scholar
  109. M. Millecamps, J. T. Czerminski, A. P. Mathieu, and L. S. Stone, “Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model,” The Spine Journal, vol. 15, no. 12, pp. 2524–2537, 2015. View at Publisher · View at Google Scholar
  110. A. Lai, A. Moon, D. Purmessur et al., “Assessment of functional and behavioral changes sensitive to painful disc degeneration,” Journal of Orthopaedic Research, vol. 33, no. 5, pp. 755–764, 2015. View at Publisher · View at Google Scholar · View at Scopus
  111. K. Olmarker, “Puncture of a lumbar intervertebral disc induces changes in spontaneous pain behavior: an experimental study in rats,” Spine, vol. 33, no. 8, pp. 850–855, 2008. View at Publisher · View at Google Scholar · View at Scopus
  112. K. Omarker and R. R. Myers, “Pathogenesis of sciatic pain: role of herniated nucleus pulposus and deformation of spinal nerve root and dorsal root ganglion,” Pain, vol. 78, no. 2, pp. 99–105, 1998. View at Publisher · View at Google Scholar · View at Scopus
  113. N. E. Easley, M. Wang, L. M. McGrady, and J. M. Toth, “Biomechanical and radiographic evaluation of an ovine model for the human lumbar spine,” Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, vol. 222, no. 6, pp. 915–922, 2008. View at Publisher · View at Google Scholar · View at Scopus