Potential regenerative treatment strategies for intervertebral disc degeneration in dogs

BMC Veterinary Research

Volumn 10, Issue , 2014, Pages

  Bach, Frances C ^a   Willems, Nicole ^a   Penning, Louis C ^a   Ito, Keita ^b,c   Meij, Björn P ^a   Tryfonidou, Marianna A ^a  

^a UTRECHT UNIVERSITY   (Netherlands)

^b EINDHOVEN UNIVERSITY OF TECHNOLOGY   (Netherlands)

^c UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

Degeneration; Dog; Intervertebral disc; Mesenchymal stem cell; Notochordal cell; Regenerative medicine; Spine

Indexed keywords

ANIMAL; ANIMAL DISEASE; DOG; DOG DISEASE; INTERVERTEBRAL DISK DEGENERATION; METHODOLOGY; REGENERATIVE MEDICINE; REVIEW;

ANIMALS; DOG DISEASES; DOGS; INTERVERTEBRAL DISC DEGENERATION; REGENERATIVE MEDICINE;

ANIMALIA; CANIS FAMILIARIS;

EID: 84891533648     PISSN: None     EISSN: 17466148     Source Type: Journal    
DOI: 10.1186/1746-6148-10-3     Document Type: Review

References (98)

1. Risbud MV, Schaer TP, Shapiro IM. Toward an understanding of the role of notochordal cells in the adult intervertebral disc: from discord to accord. Dev Dyn 2010, 239(8):2141-2148. 10.1002/dvdy.22350, 3634351, 20568241.
2. Bergknut N, Smolders LA, Grinwis GC, Hagman R, Lagerstedt AS, Hazewinkel HA, Tryfonidou MA, Meij BP. Intervertebral disc degeneration in the dog. Part 1: Anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration. Vet J 2013, 195(3):282-291. 10.1016/j.tvjl.2012.10.024, 23177522.
3. Risbud MV, Shapiro IM. Notochordal cells in the adult intervertebral disc: new perspective on an old question. Crit Rev Eukaryot Gene Expr 2011, 21(1):29-41. 10.1615/CritRevEukarGeneExpr.v21.i1.30, 3187872, 21967331.
4. Hunter CJ, Matyas JR, Duncan NA. Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison. J Anat 2004, 205(5):357-362. 10.1111/j.0021-8782.2004.00352.x, 1571361, 15575884.
5. Smolders LA, Bergknut N, Grinwis GC, Hagman R, Lagerstedt AS, Hazewinkel HA, Tryfonidou MA, Meij BP. Intervertebral disc degeneration in the dog. Part 2: Chondrodystrophic and non-chondrodystrophic breeds. Vet J 2013, 195(3):292-299. 10.1016/j.tvjl.2012.10.011, 23154070.
6. Bergknut N, Meij BP, Hagman R, de Nies KS, Rutges JP, Smolders LA, Creemers LB, Lagerstedt AS, Hazewinkel HA, Grinwis GC. Intervertebral disc disease in dogs - part 1: a new histological grading scheme for classification of intervertebral disc degeneration in dogs. Vet J 2013, 195(2):156-163. 10.1016/j.tvjl.2012.05.027, 22789628.
7. Sakai D, Mochida J, Yamamoto Y, Nomura T, Okuma M, Nishimura K, Nakai T, Ando K, Hotta T. Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 2003, 24(20):3531-3541. 10.1016/S0142-9612(03)00222-9, 12809782.
8. Hunter CJ, Matyas JR, Duncan NA. The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. Tissue Eng 2003, 9(4):667-677. 10.1089/107632703768247368, 13678445.
9. Bergknut N, Rutges JP, Kranenburg HJ, Smolders LA, Hagman R, Smidt HJ, Lagerstedt AS, Penning LC, Voorhout G, Hazewinkel HA, Grinwis GC, Creemers LB, Meij BP, Dhert WJ. The dog as an animal model for intervertebral disc degeneration?. Spine (Phila Pa 1976) 2012, 37(5):351-358. 10.1097/BRS.0b013e31821e5665, 21544011.
10. Erwin WM, Islam D, Eftekarpour E, Inman RD, Karim MZ, Fehlings MG. Intervertebral disc-derived stem cells: implications for regenerative medicine and neural repair. Spine (Phila Pa 1976) 2013, 38(3):211-216. 10.1097/BRS.0b013e318266a80d, 22772571.
11. Meij BP, Bergknut N. Degenerative lumbosacral stenosis in dogs. Vet Clin North Am Small Anim Pract 2010, 40(5):983-1009. 10.1016/j.cvsm.2010.05.006, 20732601.
12. Smolders LA, Kingma I, Bergknut N, van der Veen AJ, Dhert WJ, Hazewinkel HA, van Dieen JH, Meij BP. Biomechanical assessment of the effects of decompressive surgery in non-chondrodystrophic and chondrodystrophic canine multisegmented lumbar spines. Eur Spine J 2012, 21(9):1692-1699. 10.1007/s00586-012-2285-0, 3459126, 22492242.
13. Sakai D, Nakai T, Mochida J, Alini M, Grad S. Differential phenotype of intervertebral disc cells: microarray and immunohistochemical analysis of canine nucleus pulposus and anulus fibrosus. Spine (Phila Pa 1976) 2009, 34(14):1448-1456. 10.1097/BRS.0b013e3181a55705, 19525835.
14. Smolders LA, Meij BP, Onis D, Riemers FM, Bergknut N, Wubbolts R, Grinwis GC, Houweling M, Groot Koerkamp MJ, van Leenen D, Holstege FC, Hazewinkel HA, Creemers LB, Penning LC, Tryfonidou MA. Gene expression profiling of early intervertebral disc degeneration reveals a down-regulation of canonical Wnt signaling and caveolin-1 expression: implications for development of regenerative strategies. Arthritis Res Ther 2013, 15(1):R23. 10.1186/ar4157, 3672710, 23360510.
15. van Dijk BG, Potier E, Ito K. Long-term culture of bovine nucleus pulposus explants in a native environment. Spine J 2013, 13(4):454-463. 10.1016/j.spinee.2012.12.006, 23340344.
16. Urban JP, Maroudas A. Swelling of the intervertebral disc in vitro. Connect Tissue Res 1981, 9(1):1-10. 10.3109/03008208109160234, 6456121.
17. van Dijk B, Potier E, Ito K. Culturing bovine nucleus pulposus explants by balancing medium osmolarity. Tissue Eng Part C Methods 2011, 17(11):1089-1096. 10.1089/ten.tec.2011.0215, 21718168.
18. Gantenbein B, Grunhagen T, Lee CR, van Donkelaar CC, Alini M, Ito K. An in vitro organ culturing system for intervertebral disc explants with vertebral endplates: a feasibility study with ovine caudal discs. Spine (Phila Pa 1976) 2006, 31(23):2665-2673. 10.1097/01.brs.0000244620.15386.df, 17077734.
19. Illien-Junger S, Gantenbein-Ritter B, Grad S, Lezuo P, Ferguson SJ, Alini M, Ito K. The combined effects of limited nutrition and high-frequency loading on intervertebral discs with endplates. Spine (Phila Pa 1976) 2010, 35(19):1744-1752. 10.1097/BRS.0b013e3181c48019, 20395884.
20. Alini M, Eisenstein SM, Ito K, Little C, Kettler AA, Masuda K, Melrose J, Ralphs J, Stokes I, Wilke HJ. Are animal models useful for studying human disc disorders/degeneration?. Eur Spine J 2008, 17(1):2-19. 10.1007/s00586-007-0414-y, 2365516, 17632738.
21. Ganey T, Libera J, Moos V, Alasevic O, Fritsch KG, Meisel HJ, Hutton WC. Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine (Phila Pa 1976) 2003, 28(23):2609-2620. 10.1097/01.BRS.0000097891.63063.78, 14652478.
22. 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(1):5-21. 10.1016/j.bioeng.2006.07.002, 16963315.
23. Hohaus C, Ganey TM, Minkus Y, Meisel HJ. Cell transplantation in lumbar spine disc degeneration disease. Eur Spine J 2008, 17(4):492-503. 2587656, 19005697.
24. Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K, Tamura F, Sakai D. Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res 2008, 26(5):589-600. 10.1002/jor.20584, 18203202.
25. Ganey T, Hutton WC, Moseley T, Hedrick M, Meisel HJ. Intervertebral disc repair using adipose tissue-derived stem and regenerative cells: experiments in a canine model. Spine (Phila Pa 1976) 2009, 34(21):2297-2304. 10.1097/BRS.0b013e3181a54157, 19934809.
26. Serigano K, Sakai D, Hiyama A, Tamura F, Tanaka M, Mochida J. Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. J Orthop Res 2010, 28(10):1267-1275. 10.1002/jor.21147, 20839317.
27. Henriksson HB, Brisby H. Development and regeneration potential of the mammalian intervertebral disc. Cells Tissues Organs 2013, 197(1):1-13. 10.1159/000341153, 22965025.
28. Nomura T, Mochida J, Okuma M, Nishimura K, Sakabe K. Nucleus pulposus allograft retards intervertebral disc degeneration. Clin Orthop Relat Res 2001, 389:94-101.
29. Nishimura K, Mochida J. Percutaneous reinsertion of the nucleus pulposus. An experimental study. Spine (Phila Pa 1976) 1998, 23(14):1531-1538. 10.1097/00007632-199807150-00006, 9682309.
30. 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, 17(11):1959-1966. 10.1038/mt.2009.146, 2835041, 19584814.
31. Takada T, Nishida K, Doita M, Kurosaka M. Fas ligand exists on intervertebral disc cells: a potential molecular mechanism for immune privilege of the disc. Spine (Phila Pa 1976) 2002, 27(14):1526-1530. 10.1097/00007632-200207150-00009, 12131712.
32. Watanabe T, Sakai D, Yamamoto Y, Iwashina T, Serigano K, Tamura F, Mochida J. 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(5):623-630.
33. Okuma M, Mochida J, Nishimura K, Sakabe K, Seiki K. Reinsertion of stimulated nucleus pulposus cells retards intervertebral disc degeneration: an in vitro and in vivo experimental study. J Orthop Res 2000, 18(6):988-997. 10.1002/jor.1100180620, 11192261.
34. Yamamoto Y, Mochida J, Sakai D, Nakai T, Nishimura K, Kawada H, Hotta T. 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) 2004, 29(14):1508-1514. 10.1097/01.BRS.0000131416.90906.20, 15247571.
35. 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. Adipose-derived stem cell therapy for intervertebral disc regeneration: an in vitro reconstructed tissue in alginate capsules. Tissue Eng Part A 2008, 14(8):1415-1423. 10.1089/ten.tea.2007.0330, 18593270.
36. Lu ZF, Zandieh Doulabi B, Wuisman PI, Bank RA, Helder MN. Differentiation of adipose stem cells by nucleus pulposus cells: configuration effect. Biochem Biophys Res Commun 2007, 359(4):991-996. 10.1016/j.bbrc.2007.06.002, 17572383.
37. Mochida J. New strategies for disc repair: novel preclinical trials. J Orthop Sci 2005, 10(1):112-118. 10.1007/s00776-004-0864-6, 15666134.
38. Svanvik T, Henriksson HB, Karlsson C, Hagman M, Lindahl A, Brisby H. Human disk cells from degenerated disks and mesenchymal stem cells in co-culture result in increased matrix production. Cells Tissues Organs 2010, 191(1):2-11. 10.1159/000223236, 19494482.
39. Yang SH, Wu CC, Shih TT, Sun YH, Lin FH. In vitro study on interaction between human nucleus pulposus cells and mesenchymal stem cells through paracrine stimulation. Spine (Phila Pa 1976) 2008, 33(18):1951-1957. 10.1097/BRS.0b013e31817e6974, 18708927.
40. Acharya C, Adesida A, Zajac P, Mumme M, Riesle J, Martin I, Barbero A. Enhanced chondrocyte proliferation and mesenchymal stromal cells chondrogenesis in coculture pellets mediate improved cartilage formation. J Cell Physiol 2012, 227(1):88-97. 10.1002/jcp.22706, 22025108.
41. McCann MR, Bacher CA, Seguin CA. Exploiting notochord cells for stem cell-based regeneration of the intervertebral disc. J Cell Commun Signal 2011, 5(1):39-43. 10.1007/s12079-010-0116-9, 3058196, 21484587.
42. Chen S, Emery SE, Pei M. Coculture of synovium-derived stem cells and nucleus pulposus cells in serum-free defined medium with supplementation of transforming growth factor-beta1: a potential application of tissue-specific stem cells in disc regeneration. Spine (Phila Pa 1976) 2009, 34(12):1272-1280. 10.1097/BRS.0b013e3181a2b347, 19455002.
43. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002, 30(1):42-48. 10.1016/S0301-472X(01)00769-X, 11823036.
44. Meirelles Lda S, Fontes AM, Covas DT, Caplan AI. Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 2009, 20(5-6):419-427.
45. Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003, 75(3):389-397. 10.1097/01.TP.0000045055.63901.A9, 12589164.
46. Strassburg S, Hodson NW, Hill PI, Richardson SM, Hoyland JA. Bi-directional exchange of membrane components occurs during co-culture of mesenchymal stem cells and nucleus pulposus cells. PLoS One 2012, 7(3):e33739. 10.1371/journal.pone.0033739, 3305345, 22438989.
47. Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, Berven S. Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 2004, 32(3):430-434.
48. Sakai D, Mochida J, Iwashina T, Hiyama A, Omi H, Imai M, Nakai T, Ando K, Hotta T. Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 2006, 27(3):335-345. 10.1016/j.biomaterials.2005.06.038, 16112726.
49. Zhang YG, Guo X, Xu P, Kang LL, Li J. Bone mesenchymal stem cells transplanted into rabbit intervertebral discs can increase proteoglycans. Clin Orthop Relat Res 2005, 430:219-226.
50. Sakai D, Mochida J, Iwashina T, Watanabe T, Nakai T, Ando K, Hotta T. 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) 2005, 30(21):2379-2387. 10.1097/01.brs.0000184365.28481.e3, 16261113.
51. Chun HJ, Kim YS, Kim BK, Kim EH, Kim JH, Do BR, Hwang SJ, Hwang JY, Lee YK. Transplantation of human adipose-derived stem cells in a rabbit model of traumatic degeneration of lumbar discs. World Neurosurg 2012, 78(3-4):364-371.
52. Jin ES, Min J, Jeon SR, Choi KH, Jeong JH. Analysis of molecular expression in adipose tissue-derived mesenchymal stem cells: prospects for use in the treatment of intervertebral disc degeneration. J Korean Neurosurg Soc 2013, 53(4):207-212. 10.3340/jkns.2013.53.4.207, 3698229, 23826475.
53. Steck E, Bertram H, Abel R, Chen B, Winter A, Richter W. Induction of intervertebral disc-like cells from adult mesenchymal stem cells. Stem Cells 2005, 23(3):403-411. 10.1634/stemcells.2004-0107, 15749935.
54. Bertolo A, Mehr M, Aebli N, Baur M, Ferguson SJ, Stoyanov JV. Influence of different commercial scaffolds on the in vitro differentiation of human mesenchymal stem cells to nucleus pulposus-like cells. Eur Spine J 2012, 21:826-838.
55. 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(1):85-93. 10.1016/j.biomaterials.2007.09.018, 17920676.
56. Sakai D, Nakamura Y, Nakai T, Mishima T, Kato S, Grad S, Alini M, Risbud MV, Chan D, Cheah KS, Yamamura K, Masuda K, Okano H, Ando K, Mochida J. Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc. Nat Commun 2012, 3:1264. 3535337, 23232394.
57. Huang S, Leung VY, Long D, Chan D, Lu WW, Cheung KM, Zhou G. Coupling of small leucine-rich proteoglycans to hypoxic survival of a progenitor cell-like subpopulation in Rhesus Macaque intervertebral disc. Biomaterials 2013, 34(28):6548-6558. 10.1016/j.biomaterials.2013.05.027, 23764115.
58. Kim JH, Deasy BM, Seo HY, Studer RK, Vo NV, Georgescu HI, Sowa GA, Kang JD. Differentiation of intervertebral notochordal cells through live automated cell imaging system in vitro. Spine (Phila Pa 1976) 2009, 34(23):2486-2493. 10.1097/BRS.0b013e3181b26ed1, 19841610.
59. Korecki CL, Taboas JM, Tuan RS, Iatridis JC. Notochordal cell conditioned medium stimulates mesenchymal stem cell differentiation toward a young nucleus pulposus phenotype. Stem Cell Res Ther 2010, 1(2):18. 10.1186/scrt18, 2905094, 20565707.
60. Purmessur D, Schek RM, Abbott RD, Ballif BA, Godburn KE, Iatridis JC. Notochordal conditioned media from tissue increases proteoglycan accumulation and promotes a healthy nucleus pulposus phenotype in human mesenchymal stem cells. Arthritis Res Ther 2011, 13(3):R81. 10.1186/ar3344, 3218891, 21627827.
61. Abbott RD, Purmessur D, Monsey RD, Iatridis JC. Regenerative potential of TGFbeta3 + Dex and notochordal cell conditioned media on degenerated human intervertebral disc cells. J Orthop Res 2012, 30(3):482-488. 10.1002/jor.21534, 3264846, 21866573.
62. Aguiar DJ, Johnson SL, Oegema TR. Notochordal cells interact with nucleus pulposus cells: regulation of proteoglycan synthesis. Exp Cell Res 1999, 246(1):129-137. 10.1006/excr.1998.4287, 9882522.
63. Erwin WM, Inman RD. Notochord cells regulate intervertebral disc chondrocyte proteoglycan production and cell proliferation. Spine (Phila Pa 1976) 2006, 31(10):1094-1099. 10.1097/01.brs.0000216593.97157.dd, 16648742.
64. Allon AA, Butcher K, Schneider RA, Lotz JC. Structured coculture of mesenchymal stem cells and disc cells enhances differentiation and proliferation. Cells Tissues Organs 2012, 196(2):99-106. 10.1159/000332985, 3641838, 22378296.
65. Xie LW, Fang H, Chen AM, Li F. Differentiation of rat adipose tissue-derived mesenchymal stem cells towards a nucleus pulposus-like phenotype in vitro. Chin J Traumatol 2009, 12(2):98-103.
66. Erwin WM, Islam D, Inman RD, Fehlings MG, Tsui FW. Notochordal cells protect nucleus pulposus cells from degradation and apoptosis: implications for the mechanisms of intervertebral disc degeneration. Arthritis Res Ther 2011, 13(6):R215. 10.1186/ar3548, 3334668, 22206702.
67. Erwin WM, Ashman K, O'Donnel P, Inman RD. Nucleus pulposus notochord cells secrete connective tissue growth factor and up-regulate proteoglycan expression by intervertebral disc chondrocytes. Arthritis Rheum 2006, 54(12):3859-3867. 10.1002/art.22258, 17136753.
68. Erwin WM. The Notochord, Notochordal cell and CTGF/CCN-2: ongoing activity from development through maturation. J Cell Commun Signal 2008, 2(3-4):59-65. 2648046, 19003520.
69. Erwin WM, Las Heras F, Islam D, Fehlings MG, Inman RD. The regenerative capacity of the notochordal cell: tissue constructs generated in vitro under hypoxic conditions. J Neurosurg Spine 2009, 10(6):513-521. 10.3171/2009.2.SPINE08578, 19558283.
70. Kim KW, Ha KY, Lee JS, Nam SW, Woo YK, Lim TH, An HS. Notochordal cells stimulate migration of cartilage end plate chondrocytes of the intervertebral disc in in vitro cell migration assays. Spine J 2009, 9(4):323-329. 10.1016/j.spinee.2008.05.003, 18619909.
71. Zavala G, Vazquez-Nin GH. Analysis of nuclear ribonucleoproteic structures during notochordal cell differentiation and maturation in chick embryos. Anat Rec 2000, 259(2):113-123. 10.1002/(SICI)1097-0185(20000601)259:2<113::AID-AR1>3.0.CO;2-V, 10820313.
72. Chen J, Yan W, Setton LA. Molecular phenotypes of notochordal cells purified from immature nucleus pulposus. Eur Spine J 2006, 15:303-311.
73. Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C, Flanagan AM. Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol 2006, 209(2):157-165. 10.1002/path.1969, 16538613.
74. Yang F, Leung VY, Luk KD, Chan D, Cheung KM. Injury-induced sequential transformation of notochordal nucleus pulposus to chondrogenic and fibrocartilaginous phenotype in the mouse. J Pathol 2009, 218(1):113-121. 10.1002/path.2519, 19288580.
75. Guehring T, Urban JP, Cui Z, Tirlapur UK. Noninvasive 3D vital imaging and characterization of notochordal cells of the intervertebral disc by femtosecond near-infrared two-photon laser scanning microscopy and spatial-volume rendering. Microsc Res Tech 2008, 71(4):298-304. 10.1002/jemt.20557, 18189326.
76. Minogue BM, Richardson SM, Zeef LA, Freemont AJ, Hoyland JA. Transcriptional profiling of bovine intervertebral disc cells: implications for identification of normal and degenerate human intervertebral disc cell phenotypes. Arthritis Res Ther 2010, 12(1):R22. 10.1186/ar2929, 2875656, 20149220.
77. Cappello R, Bird JL, Pfeiffer D, Bayliss MT, Dudhia J. Notochordal cell produce and assemble extracellular matrix in a distinct manner, which may be responsible for the maintenance of healthy nucleus pulposus. Spine (Phila Pa 1976) 2006, 31(8):873-882. 10.1097/01.brs.0000209302.00820.fd, 16622374.
78. Choi KS, Cohn MJ, Harfe BD. Identification of nucleus pulposus precursor cells and notochordal remnants in the mouse: implications for disk degeneration and chordoma formation. Dev Dyn 2008, 237(12):3953-3958. 10.1002/dvdy.21805, 2646501, 19035356.
79. McCann MR, Tamplin OJ, Rossant J, Seguin CA. Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development. Dis Model Mech 2012, 5(1):73-82. 10.1242/dmm.008128, 3255545, 22028328.
80. Hoogendoorn R. Notochordal cells in mature caprine intervertebral discs. Eur Cells and Materials 2005, 10(3):59.
81. Gilson A, Dreger M, Urban JP. Differential expression level of cytokeratin 8 in cells of the bovine nucleus pulposus complicates the search for specific intervertebral disc cell markers. Arthritis Res Ther 2010, 12(1):R24. 10.1186/ar2931, 2875658, 20152014.
82. Rutges J, Creemers LB, Dhert W, Milz S, Sakai D, Mochida J, Alini M, Grad S. Variations in gene and protein expression in human nucleus pulposus in comparison with annulus fibrosus and cartilage cells: potential associations with aging and degeneration. Osteoarthritis Cartilage 2010, 18(3):416-423. 10.1016/j.joca.2009.09.009, 19833252.
83. Rastogi A, Thakore P, Leung A, Benavides M, Machado M, Morschauser MA, Hsieh AH. Environmental regulation of notochordal gene expression in nucleus pulposus cells. J Cell Physiol 2009, 220(3):698-705. 10.1002/jcp.21816, 19472213.
84. Masuda K. Biological repair of the degenerated intervertebral disc by the injection of growth factors. Eur Spine J 2008, 17:441-451. 10.1007/s00586-008-0749-z, 2587664, 19005698.
85. Nishida K, Doita M, Takada T, Kakutani K, Miyamoto H, Shimomura T, Maeno K, Kurosaka M. Sustained transgene expression in intervertebral disc cells in vivo mediated by microbubble-enhanced ultrasound gene therapy. Spine (Phila Pa 1976) 2006, 31(13):1415-1419. 10.1097/01.brs.0000219945.70675.dd, 16741448.
86. Nishida K, Kang JD, Gilbertson LG, Moon SH, Suh JK, Vogt MT, Robbins PD, Evans CH. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene. Spine (Phila Pa 1976) 1999, 24(23):2419-2425. 10.1097/00007632-199912010-00002, 10626303.
87. Maerz T, Herkowitz H, Baker K. Molecular and genetic advances in the regeneration of the intervertebral disc. Surg Neurol Int 2013, 4:94-S105. 3740608, 23956937.
88. Fassett DR, Kurd MF, Vaccaro AR. Biologic solutions for degenerative disk disease. J Spinal Disord Tech 2009, 22(4):297-308. 10.1097/BSD.0b013e31816d5f64, 19494751.
89. Niemansburg SL, van Delden JJ, Dhert WJ, Bredenoord AL. Regenerative medicine interventions for orthopedic disorders: ethical issues in the translation into patients. Regen Med 2013, 8(1):65-73. 10.2217/rme.12.112, 23259806.
90. Ho G, Leung VY, Cheung KM, Chan D. Effect of severity of intervertebral disc injury on mesenchymal stem cell-based regeneration. Connect Tissue Res 2008, 49(1):15-21. 10.1080/03008200701818595, 18293174.
91. Vadala G, Sowa G, Hubert M, Gilbertson LG, Denaro V, Kang JD. Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation. J Tissue Eng Regen Med 2012, 6(5):348-355. 10.1002/term.433, 21671407.
92. Huang KY, Yan JJ, Hsieh CC, Chang MS, Lin RM. The in vivo biological effects of intradiscal recombinant human bone morphogenetic protein-2 on the injured intervertebral disc: an animal experiment. Spine (Phila Pa 1976) 2007, 32(11):1174-1180. 10.1097/01.brs.0000263369.95182.19, 17495773.
93. Walsh AJ, Bradford DS, Lotz JC. In vivo growth factor treatment of degenerated intervertebral discs. Spine (Phila Pa 1976) 2004, 29(2):156-163. 10.1097/01.BRS.0000107231.67854.9F, 14722406.
94. Wallach CJ, Kim JS, Sobajima S, Lattermann C, Oxner WM, McFadden K, Robbins PD, Gilbertson LG, Kang JD. Safety assessment of intradiscal gene transfer: a pilot study. Spine J 2006, 6(2):107-112. 10.1016/j.spinee.2005.05.002, 16517379.
95. Vadala G, Sowa GA, Kang JD. Gene therapy for disc degeneration. Expert Opin Biol Ther 2007, 7(2):185-196. 10.1517/14712598.7.2.185, 17250457.
96. Mehrkens A, Muller AM, Valderrabano V, Scharen S, Vavken P. Tissue engineering approaches to degenerative disc disease-a meta-analysis of controlled animal trials. Osteoarthritis Cartilage 2012, 20(11):1316-1325. 10.1016/j.joca.2012.06.001, 22789805.
97. Freemont AJ. The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology (Oxford) 2009, 48(1):5-10.
98. Orozco L, Soler R, Morera C, Alberca M, Sanchez A, Garcia-Sancho J. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 2011, 92(7):822-828. 10.1097/TP.0b013e3182298a15, 21792091.