Organ culture bioreactors – platforms to study human intervertebral disc degeneration and regenerative therapy

Current Stem Cell Research and Therapy

Volumn 10, Issue 4, 2015, Pages 339-352

  Gantenbein, Benjamin ^a   Illien Jünger, Svenja ^b   Chan, Samantha C W ^a,c   Walser, Jochen ^c   Haglund, Lisbet ^d   Ferguson, Stephen J ^c   Iatridis, James C ^e   Grad, Sibylle ^f  

^a UNIVERSITY OF BERN   (Switzerland)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^c SWISS FEDERAL LABORATORIES FOR MATERIALS SCIENCE AND TECHNOLOGY   (Switzerland)

^d ETH ZURICH   (Switzerland)

^e MCGILL UNIVERSITY   (Canada)

^f AO RESEARCH INSTITUTE   (Switzerland)

Author keywords

Bioreactor; Cell viability; Engineering; Intervertebral disc; Mechanical loading; Mesenchymal stem cell; Nutrition; Torsional loading

Indexed keywords

BIOMATERIAL; CYTOKINE; PEPTIDE;

ARTICLE; BIOREACTOR; COCCYGEAL BONE; ENDPLATE FRACTURE; ENZYMATIC DISC DEGENERATION; EX VIVO STUDY; FRACTURE; HUMAN; IMMUNE RESPONSE; IN VITRO STUDY; IN VIVO STUDY; INTERVERTEBRAL DISK DEGENERATION; LUMBAR SPINE; MECHANICAL DISC DEGENERATION; NONHUMAN; ORGAN CULTURE; PAIN ASSESSMENT; PRIORITY JOURNAL; REGENERATIVE MEDICINE; STEM CELL TRANSPLANTATION; ANIMAL; CYTOLOGY; INTERVERTEBRAL DISC DEGENERATION; INTERVERTEBRAL DISK; MESENCHYMAL STROMA CELL; ORGAN CULTURE TECHNIQUE;

ANIMALS; BIOCOMPATIBLE MATERIALS; BIOREACTORS; HUMANS; INTERVERTEBRAL DISC; INTERVERTEBRAL DISC DEGENERATION; MESENCHYMAL STROMAL CELLS; ORGAN CULTURE TECHNIQUES;

EID: 84930512829     PISSN: 1574888X     EISSN: None     Source Type: Journal    
DOI: 10.2174/1574888X10666150312102948     Document Type: Article

References (135)

1. Wieser S, Horisberger B, Schmidhauser S, et al. Cost of low back pain in Switzerland in 2005. Eur J Health Econ 2011; 12:455-67.
2. Ricci JA, Stewart WF, Chee E, et al. Back pain exacerbations and lost productive time costs in United States workers. Spine (Phila Pa 1976) 2006; 31: 3052-60.
3. Adams MA, Dolan P. Could sudden increases in physical activity cause degeneration of intervertebral discs? Lancet 1997; 350: 734-5.
4. Adams MA, Freeman BJ, Morrison HP, et al. Mechanical initiation of intervertebral disc degeneration Spine 2000; 25: 1625-36.
5. Grunhagen T, Shirazi-Adl A, Fairbank JC, et al. Intervertebral disk nutrition: a review of factors influencing concentrations of nutrients and metabolites. Orthop Clin North Am 2011; 42: 465-77.
6. Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebral disc. Spine 2004; 29: 2700-9.
7. Paul CP, Schoorl T, Zuiderbaan HA, et al. Dynamic and static overloading induce early degenerative processes in caprine lumbar intervertebral discs. PLoS ONE 2013; 8: e62411.
8. Bibby SR, Jones DA, Ripley RM, et al. Metabolism of the intervertebral disc: effects of low levels of oxygen, glucose, and pH on rates of energy metabolism of bovine nucleus pulposus cells Spine 2005; 30: 487-96.
9. Bibby SR, Urban JP. Effect of nutrient deprivation on the viability of intervertebral disc cells. Eur Spine J 2004; 13: 695-701.
10. van der Werf M, Lezuo P, Maissen O, et al. Inhibition of vertebral endplate perfusion results in decreased intervertebral disc intranuclear diffusive transport. J Anat 2007; 211: 769-74.
11. Hutton WC, Murakami H, Li J, et al. The effect of blocking a nutritional pathway to the intervertebral disc in the dog model Journal of Spinal Disorders 2004; 17: 53-63.
12. Alini M, Eisenstein SM, Ito K, et al. Are animal models useful for studying human disc disorders/degeneration? Eur Spine J 2008; 17: 2-19.
13. Busscher I, van der Veen AJ, van Dieën JH, et al. In vitro biomechanical characteristics of the spine: a comparison between human and porcine spinal segments. Spine (Phila Pa 1976) 2010; 35: E35-42.
14. van Deursen DL, Snijders CJ, Kingma I, et al. In vitro torsioninduced stress distribution changes in porcine intervertebral discs. Spine (Phila Pa 1976) 2001; 26: 2582-6.
15. Omlor GW, Bertram H, Kleinschmidt K, et al. Methods to monitor distribution and metabolic activity of mesenchymal stem cells following in vivo injection into nucleotomized porcine intervertebral discs. Eur Spine J 2010; 19: 601-12.
16. Kobayashi S, Meir A, Urban J. Effect of cell density on the rate of glycosaminoglycan accumulation by disc and cartilage cells in vitro. J Orthop Res 2008; 26: 493-503.
17. Miyazaki T, Kobayashi S, Takeno K, et al. A Phenotypic Comparison of Proteoglycan Production of Intervertebral Disc Cells Isolated from Rats, Rabbits, and Bovine Tails; Which Animal Model is Most Suitable to Study Tissue Engineering and Biological Repair of Human Disc Disorders? Tissue Eng Part A 2009; 15: 3835-46.
18. Gantenbein B, Calandriello E, Wuertz-Kozak K, et al. Activation of intervertebral disc cells by co-culture with notochordal cells, conditioned medium and hypoxia BMC Musculoskeletal Disorders 2014; 15: 422.
19. Showalter BL, Beckstein JC, Martin JT, et al. Comparison of Animal Discs Used in Disc Research to Human Lumbar Disc: Torsion Mechanics and Collagen Content. Spine (Phila Pa 1976) 2012; 37: E900-7.
20. Rodrigues-Pinto R, Richardson SM, Hoyland JA. An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration. Eur Spine J 2014; 23: 1803-14.
21. de Vries S, Potier E, Doeselaar MV, et al. Conditioned medium derived from notochordal cell-rich nucleus pulposus tissue stimulates matrix production by canine nucleus pulposus cells and bone marrow derived stromal cells. Tissue Eng Part A 2014; epub ahead of print.
22. Purmessur D, Guterl CC, Cho SK, et al. Dynamic pressurization induces transition of notochordal cells to a mature phenotype while retaining production of important patterning ligands from development. Arthritis Res Ther 2013; 15: R122.
23. Potier E, Ito K. Using notochordal cells of developmental origin to stimulate nucleus pulposus cells and bone marrow stromal cells for intervertebral disc regeneration. Eur Spine J 2013; 23: 679-88.
24. Purmessur D, Cornejo MC, Cho SK, et al. Notochordal Cell- Derived Therapeutic Strategies for Discogenic Back Pain. Global Spine J 2013; 3: 201-18.
25. Erwin WM, Islam D, Inman RD, et al. Notochordal cells protect nucleus pulposus cells from degradation and apoptosis: implications for the mechanisms of intervertebral disc degeneration. Arthritis Res Ther 2011; 13: R215.
26. Demers CN, Antoniou J, Mwale F. Value and limitations of using the bovine tail as a model for the human lumbar spine Spine 2004; 29: 2793-9.
27. Beckstein JC, Sen S, Schaer TP, et al. Comparison of animal discs used in disc research to human lumbar disc: axial compression mechanics and glycosaminoglycan content. Spine (Phila Pa 1976) 2008; 33: E166-73.
28. Wilke HJ, Kettler A, Wenger KH, et al. Anatomy of the sheep spine and its comparison to the human spine Anat Rec 1997; 247: 542-55.
29. Walter BA, Illien-Jünger S, Nasser PR, et al. Development and validation of a bioreactor system for dynamic loading and me chanical characterization of whole human intervertebral discs in organ culture. J Biomech 2014; 47: 2095-101.
30. Illien-Jünger S, Gantenbein-Ritter B, Grad S, et al. The Combined Effects of Limited Nutrition and High-Frequency Loading on Intervertebral Discs With Endplates. Spine (Phila Pa 1976) 2010; 35 (19): 1744-52.
31. Paul CP, Zuiderbaan HA, Zandieh Doulabi B, et al. Simulatedphysiological loading conditions preserve biological and mechanical properties of caprine lumbar intervertebral discs in ex vivo culture. PLoS ONE 2012; 7: e33147.
32. Chan SCW, Walser J, Käppeli P, et al. Region Specific Response of Intervertebral Disc Cells to Complex Dynamic Loading: An Organ Culture Study Using a Dynamic Torsion-Compression Bioreactor. PLoS ONE 2013; 8: e72489.
33. Jim B, Steffen T, Moir J, et al. Development of an intact intervertebral disc organ culture system in which degeneration can be induced as a prelude to studying repair potential. Eur Spine J 2011; 20: 1244-54.
34. Haglund L, Moir J, Beckman L, et al. Development of a Bioreactor for Axially Loaded Intervertebral Disc Organ Culture. Tissue Eng Part C Methods 2011; 17: 1011-9.
35. Dudli S, John Ferguson S, Haschtmann D. Severity and pattern of posttraumatic intervertebral disc degeneration depends on the type of injury. Spine J 2014; epub ahead of print.
36. Gantenbein B, Grünhagen T, Lee CR, et al. 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: 2665-73.
37. Jünger S, Gantenbein-Ritter B, Lezuo P, et al. Effect of limited nutrition on in situ intervertebral disc cells under simulatedphysiological loading. Spine (Phila Pa 1976) 2009; 34: 1264-71.
38. Illien-Jünger S, Gantenbein-Ritter B, Grad S, et al. The Combined Effects of Limited Nutrition and High-Frequency Loading on Intervertebral Discs With Endplates. Spine (Phila Pa 1976) 2010; 35 (19): 1744-52.
39. Chan SCW, Gantenbein-Ritter B, Leung VY, et al. Cryopreserved intervertebral disc with injected bone marrow-derived stromal cells: a feasibility study using organ culture. Spine J 2010; 10(6): 486-96.
40. Chan SC, Gantenbein-Ritter B. Preparation of intact bovine tail intervertebral discs for organ culture. J Vis Exp 2012; 60: e3490.
41. Walser J, Ferguson SJ, Gantenbein-Ritter B. Design of a mechanical loading device to Culture intact Bovine Caudal Motional Segments of the Spine under Twisting Motion. In: Davies J, ed. Replacing animal models: a practical guide to creating and using biomimetic alternatives. Chichester, UK, John Wiley & Sons, Ltd., 2012; pp. 89-105.
42. Bailey JF, Hargens AR, Cheng KK, et al. Effect of microgravity on the biomechanical properties of lumbar and caudal intervertebral discs in mice. J Biomech 2014; 47: 2983-8.
43. Jin L, Feng G, Reames DL, et al. The effects of simulated microgravity on intervertebral disc degeneration. Spine J 2013; 13: 235-42.
44. Ohshima H, Tsuji H, Hirano N, et al. Water diffusion pathway, swelling pressure, and biomechanical properties of the intervertebral disc during compression load. Spine 1989; 14: 1234-44.
45. Walter BA, Korecki CL, Purmessur D, et al. Complex loading affects intervertebral disc mechanics and biology. Osteoarthritis Cartilage 2011; 19: 1011-8.
46. Adams MA, Hutton WC. Prolapsed intervertebral disc. A hyperflexion injury 1981 Volvo Award in Basic Science. Spine (Phila Pa 1976) 1982; 7: 184-91.
47. Dudli S, Haschtmann D, Ferguson SJ. Persistent degenerative changes in the intervertebral disc after burst fracture in an in vitro model mimicking physiological post-traumatic conditions. Eur Spine J 2014; epub ahead of print.
48. Lawless IM, Ding B, Cazzolato BS, et al. Adaptive velocity-based six degree of freedom load control for real-time unconstrained biomechanical testing. J Biomech 2014; 47: 3241-7.
49. Vergroesen P-PA, Veen AJVD, Royen BJV, et al. Intradiscal pressure depends on recent loading and correlates with disc height and compressive stiffness. European Spine Journal 2014; 23: 2359-68.
50. Castro APG, Paul CPL, Detiger SEL, et al. Long-Term Creep Behavior of the Intervertebral Disk: Comparison between Bioreactor Data and Numerical Results. Frontiers in Bioengineering and Biotechnology 2014; 2.
51. Paul CP, Strijkers GJ, de Graaf M, et al. Changes in Biomechanical, Histological and Quantitative MRI Parameters in Lumbar Caprine Intervertebral Discs Subjected to Chondroitinase-Induced Degeneration. Global Spine Journal 2012; 2: P86.
52. White AA, Panjabi MM. Clinical Biomechanics of the Spine; Philadelphia, Pennsylvania: B Lippincott Company, 1990.
53. Oshima H, Ishihara H, Urban JP, et al. The use of coccygeal discs to study intervertebral disc metabolism. J Orthop Res 1993; 11: 332-8.
54. Lee CR, Iatridis JC, Poveda L, et al. In vitro organ culture of the bovine intervertebral disc: effects of vertebral endplate and potential for mechanobiology studies. Spine (Phila Pa 1976) 2006; 31: 515-22.
55. Chiba K, Andersson GB, Masuda K, et al. A new culture system to study the metabolism of the intervertebral disc in vitro Spine 1998; 23: 1821-27.
56. Bayliss MT, Urban JP, Johnstone B, et al. In vitro method for measuring synthesis rates in the intervertebral disc. Journal of Orthopaedic Research 1986; 4: 10-17.
57. Gawri R, Mwale F, Ouellet J, et al. Development of an organ culture system for long term survival of the intact human intervertebral disc. Spine (Phila Pa 1976) 2011; 36: 1835-42.
58. van Dijk BG, Potier E, Ito K. Long-term culture of bovine nucleus pulposus explants in a native environment. Spine J 2013; epub ahead of print
59. Potier E, de Vries S, van Doeselaar M, et al. Potential application of notochordal cells for intervertebral disc regeneration: an in vitro assessment. Eur Cell Mater 2014; 28: 68-81.
60. Haschtmann D, Stoyanov JV, Ferguson SJ. Influence of diurnal hyperosmotic loading on the metabolism and matrix gene expression of a whole-organ intervertebral disc model. J Orthop Res 2006; 24: 1957-66.
61. Caplan AI. Mesenchymal stem cells. J Orthop Res 1991; 9: 641-50.
62. Evans CH. Advances in regenerative orthopedics. Mayo Clin Proc 2013; 88: 1323-39.
63. Risbud MV, Albert TJ, Guttapalli A, et al. Differentiation of mesenchymal stem cells towards a nucleus pulposus-like phenotype in vitro: implications for cell-based transplantation therapy. Spine (Phila Pa 1976) 2004; 29: 2627-32.
64. Crevensten G, Walsh AJ, Ananthakrishnan D, et al. Intervertebral disc cell therapy for regeneration: mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 2004; 32: 430-4.
65. Meisel HJ, Siodla V, Ganey T, et al. Clinical experience in cellbased therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc. Biomol Eng 2007; 24: 5-21.
66. Ganey T, Hutton WC, Moseley T, et al. Intervertebral disc repair using adipose tissue-derived stem and regenerative cells: experiments in a canine model. Spine (Phila Pa 1976) 2009; 34: 2297-304.
67. Sakai D, Mochida J, Iwashina T, 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 (Phila Pa 1976) 2005; 30: 2379-87.
68. Sakai D, Mochida J, Iwashina T, et al. Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 2006; 27: 335-45.
69. Hiyama A, Mochida J, Iwashina T, et al. Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res 2008; 26: 589-600.
70. Steck E, Bertram H, Abel R, et al. Induction of intervertebral disclike cells from adult mesenchymal stem cells. Stem Cells 2005; 23: 403-11.
71. Gantenbein-Ritter B, Benneker LM, Alini M, et al. Differential response of human bone marrow stromal cells to either TGF- b(1) or rhGDF-5. Eur Spine J 2011; 20: 962-971.
72. Stoyanov JV, Gantenbein-Ritter B, Bertolo A, et al. Role of hypoxia and growth and differentiation factor-5 on differentiation of human mesenchymal stem cells towards intervertebral nucleus pulposus-like cells. Eur Cell Mater 2011; 21: 533-47.
73. Kitaori T, Ito H, Schwarz EM, et al. Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. Arthritis Rheum 2009; 60: 813-23.
74. Illien-Jünger S, Pattappa G, Peroglio M, et al. Homing of Mesenchymal Stem Cells in Induced Degenerative Intervertebral Discs in a Whole Organ Culture System. Spine (Phila Pa 1976) 2012; 37: 1865-73.
75. Pattappa G, Peroglio M, Sakai D, et al. CCL5/RANTES is a key chemoattractant released by degenerative intervertebral discs in organ culture. Eur Cell Mater 2014; 27: 124-36 ; discussion 136.
76. Wuertz K, Godburn K, Iatridis JC. MSC response to pH levels found in degenerating intervertebral discs. Biochem Biophys Res Commun 2009; 379: 824-9.
77. Chan SC, Bürki A, Bonél HM, et al. Papain-induced in vitro disc degeneration model for the study of injectable nucleus pulposus therapy. Spine J 2013; 13: 273-83.
78. Malonzo C, Chan SCW, Kabiri A, et al. A papain-induced disc degeneration model for the assessment of thermo-reversible hydrogel- cells therapeutic approach Journal of Tissue Engineering and Regenerative Medicine 2013; epub ahead of print
79. Peroglio M, Eglin D, Benneker LM, et al. Thermoreversible hyaluronan-based hydrogel supports in vitro and ex vivo disc-like differentiation of human mesenchymal stem cells. Spine J 2013; 13: 1627-39.
80. Mwale F, Wang HT, Roughley P, et al. Link N and mesenchymal stem cells can induce regeneration of the early degenerate intervertebral disc. Tissue Eng Part A 2014; 20: 2942-9.
81. Serigano K, Sakai D, Hiyama A, et al. Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. J Orthop Res 2010; 28: 1267-75.
82. Omlor GW, Nerlich AG, Lorenz H, et al. Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model. Eur Spine J 2012; 21: 1700-8.
83. Collin EC, Grad S, Zeugolis DI, et al. An injectable vehicle for nucleus pulposus cell-based therapy. Biomaterials 2011; 32: 2862-70.
84. Cheng YH, Yang SH, Lin FH. Thermosensitive chitosan-gelatinglycerol phosphate hydrogel as a controlled release system of ferulic acid for nucleus pulposus regeneration. Biomaterials 2011; 32: 6953-61.
85. Hu J, Chen B, Guo F, et al. Injectable silk fibroin/polyurethane composite hydrogel for nucleus pulposus replacement. J Mater Sci Mater Med 2012; 23: 711-22.
86. Likhitpanichkul M, Dreischarf M, Illien-Junger S, et al. Fibringenipin adhesive hydrogel for annulus fibrosus repair: performance evaluation with large animal organ culture, in situ biomechanics, and in vivo degradation tests. Eur Cell Mater 2014; 28: 25-38.
87. Guterl CC, Torre OM, Purmessur D, et al. Characterization of Mechanics and Cytocompatibility of Fibrin-Genipin Annulus Fibrosus Sealant with the Addition of Cell Adhesion Molecules. Tissue Eng Part A 2014; epub ahead of print
88. Pereira CL, Gonçalves RM, Peroglio M, et al. The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the recruitment of MSCs in degenerating intervertebral discs. Biomaterials 2014; epub ahead of print
89. Mern DS, Beierfuß A, Thomé C, et al. Enhancing human nucleus pulposus cells for biological treatment approaches of degenerative intervertebral disc diseases: a systematic review. J Tissue Eng Regen Med 2012; epub ahead of print
90. Sakai D, Grad S. Advancing the Cellular and Molecular Therapy for Intervertebral Disc Disease. Adv Drug Deliv Rev 2014; epub ahead of print
91. Bucher C, Gazdhar A, Benneker LM, et al. Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ Culture System. Stem Cells International 2013; 2013: 326828.
92. Wallach CJ, Kim JS, Sobajima S, et al. Safety assessment of intradiscal gene transfer: a pilot study. Spine J 2006; 6: 107-12.
93. Clarke LE, McConnell JC, Sherratt MJ, et al. Growth differentiation factor 6 and transforming growth factor-beta differentially mediate mesenchymal stem cell differentiation, composition and micromechanical properties of nucleus pulposus constructs. Arthritis Res Ther 2014; 16: R67.
94. Pirvu T, Blanquer SB, Benneker LM, et al. A combined biomaterial and cellular approach for annulus fibrosus rupture repair. Biomaterials 2015; 42: 11-9.
95. Krock E, Rosenzweig DH, Haglund L. The Inflammatory Milieu of the Degenerate Disc: is Mesenchymal Stem Cell-Based Therapy for Intervertebral Disc Repair a Feasible Approach? Curr Stem Cell Res Ther 2015; epub ahead of print
96. Parolin M, Gawri R, Mwale F, et al. Development of a whole disc organ culture system to study human intervertebral disc. Evid Based Spine Care J 2010; 1: 67-8.
97. Barbir A, Godburn KE, Michalek AJ, et al. Effects of Torsion on Intervertebral Disc Gene Expression and Biomechanics, Using a Rat Tail Model. Spine (Phila Pa 1976) 2010; 36: 607-14.
98. Chan SC, Ferguson SJ, Wuertz K, et al. Biological response of the intervertebral disc to repetitive short term cyclic torsion. Spine (Phila Pa 1976) 2011; 36: 2021-30.
99. Boubriak OA, Watson N, Sivan SS, et al. Factors regulating viable cell density in the intervertebral disc: blood supply in relation to disc height. J Anat 2013; 222: 341-8.
100. Maroudas A, Stockwell RA, Nachemson A, et al. Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. J Anat 1975; 120: 113-30.
101. Kato F, Iwata H, Mimatsu K, et al. Experimental chemonucleolysis with chondroitinase ABC. Clin Orthop Relat Res 1990; 301-8.
102. Fry TR, Eurell JC, Johnson AL, et al. Radiographic and histologic effects of chondroitinase ABC on normal canine lumbar intervertebral disc. Spine (Phila Pa 1976) 1991; 16: 816-9.
103. Sugimura T, Kato F, Mimatsu K, et al. Experimental chemonucleolysis with chondroitinase ABC in monkeys. Spine (Phila Pa 1976) 1996; 21: 161-5.
104. Ishikawa H, Nohara Y, Miyauti S. Action of chondroitinase ABC on epidurally transplanted nucleus pulposus in the rabbit. Spine (Phila Pa 1976) 1999; 24: 1071-6.
105. Sakuma M, Fujii N, Takahashi T, et al. Effect of chondroitinase ABC on matrix metalloproteinases and inflammatory mediators produced by intervertebral disc of rabbit in vitro. Spine 2002; 27: 576-80.
106. Hoogendoorn RJ, Wuisman PI, Smit TH, et al. Experimental intervertebral disc degeneration induced by chondroitinase ABC in the goat. Spine (Phila Pa 1976) 2007; 32: 1816-25.
107. Hoogendoorn R, Doulabi BZ, Huang CL, et al. Molecular changes in the degenerated goat intervertebral disc. Spine 2008; 33: 1714-21.
108. Roberts S, Menage J, Sivan S, et al. Bovine explant model of degeneration of the intervertebral disc. BMC Musculoskelet Disord 2008; 9: 24.
109. Gawri R, Moir J, Ouellet J, et al. Physiological Loading Can Restore the Proteoglycan Content in a Model of Early IVD Degeneration. PLoS One 2014; 9: e101233.
110. Furtwängler T, Chan SC, Bahrenberg G, et al. Assessment of the Matrix Degenerative Effects of MMP-3, ADAMTS-4 and HTRA1 injected into a bovine Intervertebral Disc Organ Culture Model. Spine (Phila Pa 1976) 2013; 38: E1377-87.
111. Tiaden AN, Klawitter M, Lux V, et al. A detrimental role for human high temperature requirement serine protease A1 (HTRA1) in the pathogenesis of intervertebral disc (IVD) degeneration. J Biol Chem 2012; 287: 21335-45.
112. Lü DS, Shono Y, Oda I, et al. Effects of chondroitinase ABC and chymopapain on spinal motion segment biomechanics. An in vivo biomechanical, radiologic, and histologic canine study. Spine (Phila Pa 1976) 1997; 22: 1828-34; discussion 1834-5.
113. Park JS, Ahn JI. The effect of chondroitinase ABC on rabbit intervertebral disc. Radiological, histological and electron microscopic findings. Int Orthop 1995; 19: 103-9.
114. Watanabe A, Benneker LM, Boesch C, et al. Classification of intervertebral disk degeneration with axial T2 mapping. AJR Am J Roentgenol 2007; 189: 936-42.
115. Purmessur D, Walter BA, Roughley PJ, et al. A role for TNFa in intervertebral disc degeneration: a non-recoverable catabolic shift. Biochem Biophys Res Commun 2013; 433: 151-6.
116. Korecki CL, Costi JJ, Iatridis JC. Needle puncture injury affects intervertebral disc mechanics and biology in an organ culture model. Spine (Phila Pa 1976) 2008; 33: 235-41.
117. Vadalà G, Russo F, Pattappa G, et al. The transpedicular approach as an alternative route for intervertebral disc regeneration. Spine (Phila Pa 1976) 2013; 38: E319-24.
118. Peroglio M, Grad S, Mortisen D, et al. Injectable thermoreversible hyaluronan-based hydrogels for nucleus pulposus cell encapsulation. Eur Spine J 2012; 21 Suppl 6: 839-49.
119. Li Z, Kaplan KM, Wertzel A, et al. Biomimetic fibrin-hyaluronan hydrogels for nucleus pulposus regeneration. Regen Med 2014; 9: 309-26.
120. Dudli S, Haschtmann D, Ferguson SJ. Fracture of the vertebral endplates, but not equienergetic impact load, promotes disc degeneration in vitro. J Orthop Res 2011; 30: 809-16.
121. Alkhatib B, Rosenzweig DH, Krock E, et al. Acute mechanical injury of the human intervertebral disc: link to degeneration and pain. Eur Cell Mater 2014; 28: 98-110; discussion 110-1.
122. Gawri R, Antoniou J, Ouellet J, et al. Best paper NASS 2013: link- N can stimulate proteoglycan synthesis in the degenerated human intervertebral discs. Eur Cell Mater 2013; 26: 107-19; discussion 119.
123. Ariga K, Yonenobu K, Nakase T, et al. Mechanical stress-induced apoptosis of endplate chondrocytes in organ-cultured mouse intervertebral discs: an ex vivo study. Spine (Phila Pa 1976) 2003; 28: 1528-33.
124. Korecki CL, MacLean JJ, Iatridis JC. Characterization of an in vitro intervertebral disc organ culture system. Eur Spine J 2007; 16: 1029-37.
125. Illien-Jünger S, Pattappa G, Peroglio M, et al. Homing of Mesenchymal Stem Cells in Induced Degenerative Intervertebral Discs in a Whole Organ Culture System. Spine (Phila Pa 1976) 2012; 37: 1865-73.
126. Haschtmann D, Stoyanov JV, Gédet P, et al. Vertebral endplate trauma induces disc cell apoptosis and promotes organ degeneration in vitro. Eur Spine J 2008; 17: 289-99.
127. Haschtmann D, Stoyanov JV, Ettinger L, et al. Establishment of a novel intervertebral disc/endplate culture model: analysis of an ex vivo in vitro whole-organ rabbit culture system. Spine 2006; 31: 2918-25.
128. van Dijk B, Potier E, Ito K. Culturing Bovine Nucleus Pulposus Explants by Balancing Medium Osmolarity. Tissue Eng Part C Methods 2011; 17: 1089-96.
129. Risbud MV, Izzo MW, Adams CS, et al. An organ culture system for the study of the nucleus pulposus: description of the system and evaluation of the cells. Spine 2003; 28: 2652-2658.
130. Risbud MV, Di Martino A, Guttapalli A, et al. Toward an optimum system for intervertebral disc organ culture: TGF-beta3 enhances nucleus pulposus and anulus fibrosus survival and function through modulation of TGF-beta-R expression and ERK signaling. Spine 2006; 31: 884-90.
131. Chiba K, Masuda K, Andersson GB, et al. Matrix replenishment by intervertebral disc cells after chemonucleolysis in vitro with chondroitinase ABC and chymopapain. Spine J 2007; 7: 694-700.
132. Yerramalli CS, Chou AI, Miller GJ, et al. The effect of nucleus pulposus crosslinking and glycosaminoglycan degradation on disc mechanical function. Biomech Model Mechanobiol 2007; 6: 13-20.
133. Iatridis JC, Nicoll SB, Michalek AJ, et al. Role of biomechanics in intervertebral disc degeneration and regenerative therapies: what needs repairing in the disc and what are promising biomaterials for its repair? Spine J 2013; 13: 243-62.
134. Michalek AJ, Funabashi KL, Iatridis JC. Needle puncture injury of the rat intervertebral disc affects torsional and compressive biomechanics differently. Eur Spine J 2010; 19: 2110-16.
135. Iatridis JC, Michalek AJ, Purmessur D, et al. Localized Intervertebral Disc Injury Leads to Organ Level Changes in Structure, Cellularity, and Biosynthesis. Cell Mol Bioeng 2009; 2: 437-47.