Cell technologies in treatment of human intervertebral disc hernia: perspectives

Home/2015, Vol. 3, No. 2/Cell technologies in treatment of human intervertebral disc hernia: perspectives

Cell and Organ Transplantology. 2015; 3(2): 202-207.
DOI: 10.22494/COT.V3I2.15

Cell technologies in treatment of human intervertebral disc hernia: perspectives

Ustymenko A. M.
State Institute of Genetic and Regenerative Medicine NAMS of Ukraine, Kyiv, Ukraine

The intervertebral disc hernia is distinguished one of the diseases of the human locomotor apparatus that causes pain, neurological deficit and functional disorders.
Inefficency of concervative treatment and repeated appeals for medical help after surgery have urged on the need for exploration of some new more effective methods of treatment aimed not only at weakening degenerative processes and pain but also at renewing disc function and its height maintenance. Achievements of regenerative medicine and tissue engineering promote development of new efficient methods of cell therapy. The results of their application in experimental studies on animals give us hope for their successful use in humans.

Key words: intervertebral disc, nucleus pulposus, annulus fibrosus, mesenchymal stem cells, cell therapy

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1. Katz JN. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J Bone Joint Surg Am. 2006; 88(2):21-24.
2. Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. The Lancet. 2010; 380(9859):2163–2196.
3. Dagenais S, Tricco A, Haldeman S. Synthesis of recommendations for the assessment and management of low back pain from recent clinical practice guidelines. Spine Journal. 2010; 10(6):514–529.
4. Shamji MF, Setton LA, Jarvis V, et al. Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues. Arthritis Rheum. 2010; 62:1974–1982.
PMid:20222111 PMCid:PMC2917579
5. Risbud MV, Shapiro IM. Role of Cytokines in Intervertebral Disc Degeneration: Pain and Disc-content. Nat Rev Rheumatol. 2014; 10(1):44–56.
PMid:24166242 PMCid:PMC4151534
6. Molinos M, Almeida CR, Caldeira J, et al. Inflammation in intervertebral disc degeneration and regeneration. J. R. Soc. 2015; 12: 20141191.
PMid:25673296 PMCid:PMC4345483
7. Melrose J, Roberts S, Smith S, et al. Increased nerve and blood vessel ingrowth associated with proteoglycan depletion in an ovine anular lesion model of experimental disc degeneration. Spine. 2002; 27:1278–1285.
8. Freemont AJ, Watkins A, Le Maitre C, et al. Nerve growth factor expression and innervation of the painful intervertebral disc. J Pathol. 2002; 197: 286–292.
9. Atlas SJ, Keller RB, Wu Y A, et al. Long-term outcomes of surgical and nonsurgical management of sciatica secondary to a lumbar disc herniation: 10 year results from the maine lumbar spine study. Spine. 2005; 30(8):927–935.
10. Choy DS. Familial incidence of intervertebral disc herniation: an hypothesis suggesting that laminectomy and discectomy may be counterproductive. J Clin Laser Med Surg. 2000; 18(1):29–32.
11. Hakkinen A, Kiviranta I, Neva MH, et al. Reoperations after first lumbar disc herniation surgery; a special interest on residives during a 5-year follow-up. BMC Musculoskelet Disord. 2007; 8(2):DOI:10.1186/1471-2474-8-2.
12. Swartz KR, Trost GR. Recurrent lumbar disc herniation. Neurosurg Focus. 2003; 15(3):P. E10.
13. Xia XP, Chen HL, Cheng HB. Prevalence of adjacent segment degeneration after spine surgery: a systematic review and meta-analysis. Spine. 2013; 38:597–608.
14. Mochida J, Nishimura K, Nomura T, et al. The importance of preserving disc structure in surgical approaches to lumbar disc herniation. Spine. 1996; 21:1556–1563.
15. Schlegel JD, Smith JA, Schleusener RL. Lumbar motion segment pathology adjacent to thoracolumbar, lumbar, and lumbosacral fusions. Spine. 1996; 21:970-981.
16. Wei A, Shen B, Williams L, et al. Mesenchymal stem cells: potential application in intervertebral disc regeneration. Translational Pediatrics. 2014; 3(2):71-90.
PMid:26835326 PMCid:PMC4729108
17. Bach FC, Willems N, Penning LC, et al. Potential regenerative treatment strategies for intervertebral disc degeneration in dogs. BMC Vet Res. 2014; 10(1):3.
PMid:24387033 PMCid:PMC3914844
18. Gilbert HT, Hoyland JA, Richardson SM. Stem cell regeneration of degenerated intervertebral discs: current status (update). Curr Pain Headache Rep. 2013; 17:377.
19. Gilchrist CL, Francisco AT, Plopper GE. Nucleus pulposus cell-matrix interactions with laminins. Eur Cell Mater. 2011; 21:523–532.
PMid:21710443 PMCid:PMC3332080
20. Hardingham TE, Muir H. The specific interaction of hyaluronic acid with cartilage proteoglycans. Biochim Biophys Acta. 1972; 279:401-405.
21. Antoniou J, Steffen T, Nelson F, et al. “The human lumbar intervertebral disc: Evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration”. Journal of Clinical Investigation. 1996; 98(4):996–1003.
PMid:8770872 PMCid:PMC507515
22. Adams MA, Hutton WC. Gradual disc prolapse. Spine.1985; 10(6):524-31.
23. Bach FC, de Vries HSA, Krouwels A. The species-specific regenerative effects of notochordal cell-conditioned medium on chondrocyte-like cells derived from degenerated human intervertebral discs. European Cells and Materials. 2015; 30:132-147.
24. Liebscher T, Haefeli M, Wuertz K, et al. Age-related variation in cell density of human lumbar inter- vertebral disc. Spine. 2011; 36:153–159.
25. Hunter CJ, Matyas JR, Duncan NA. The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. Tissue Eng. 2003; 9:667–677.
26. 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; 237:3953–3958.
PMid:19035356 PMCid:PMC2646501
27. Sivakamasundari V, Lufkin T. Stemming the Degeneration: IVD Stem Cells and Stem Cell Regenerative Therapy for Degenerative Disc Disease. Advances in Stem Cells. 2013; 2013:ID 724547.
PMid:23951558 PMCid:PMC3742038
28. Risbud MV, Shapiro I M. Notochordal Cells in the Adult Intervertebral Disc: New Perspective on an Old Question. Eukaryot Gene Expr. 2011; 21(1):29–41.
29. Pattappa G, Li Z, Peroglio M, et al. Diversity of intervertebral disc cells: phenotype and function. J. Anat. 2012; 221:480–496.
PMid:22686699 PMCid:PMC3512276
30. Walmsley R. The development and growth of the intervertebral disc. Edinburgh Med J. 1953; 60(8):341-364.
31. Roberts S, Evans H, Trivedi J, et al. Histology and pathology of the human intervertebral disc. J Bone Joint Surg. 2006; 88(2):10–14.
32. Hunter CJ, Matyas J R, Duncan NA. Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison. J Anat. 2004; 205:357-362.
PMid:15575884 PMCid:PMC1571361
33. Deduch NV. Mezhpozvonkovye diski: strukturnaja organizacija v norme i pri patologii [Intervertebral discs: structural organization in health and disease]. Problemy osteologii – Prorblems of osteology, 2008; 11(3-4):11-17.
34. Bron JL, Helder MN, Meisel H-J, et al. Repair, regenerative and supportive therapies of the annulus fibrosus: achievements and challenges. Eur Spine J. 2009;18:301–313.
PMid:19104850 PMCid:PMC2899423
35. Tomaszewski KA, Walocha JA, Mizia E, et al. Age- and degeneration-related variations in cell density and glycosaminoglycan content in the human cervical intervertebral disc and its endplates. Pol J Pathol. 2015; 66(3):296-300.
36. Risbud MV, Guttapalli A, Tsai TT, et al. Evidence for skeletal progenitor cells in the degenerate human intervertebral disc. Spine. 2007; 32(23): 2537–2544.
37. Roberts S, Menage J, Urban JP. Biochemical and structural properties of the cartilage end-plate and its relation to the intervertebral disc. Spine. 1989; 14: 166-174.
38. Adams M A, Roughley PJ. What is Intervertebral Disc Degeneration, and What Causes It? Spine. 2006; 31(18):2151-2161.
39. Brisby H, Papadimitriou N, Brantsing C, et al. The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: a descriptive study in humans. Stem Cells Dev. 2013; 22:804-14.
40. Kim KW, Ha KY, Lee JS, et al. Notochordal cells stimulate migration of cartilage end plate chondrocytes of the intervertebral disc in in vitro cell migration assays. Spine J. 2009; 9:323-9.
41. Martin JT, Milby AH, Chiaro JA, et al. Translation of an Engineered Nanofibrous Disc-like Angle Ply Structure for Intervertebral Disc Replacement in a Small Animal Model. Acta Biomater. 2014; 10(6):2473–2481.
PMid:24560621 PMCid:PMC4412172
42. 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; 32:430–434.
43. Wang YH, Yang B, Li WL, Li J. M. Effect of the mixture of bone marrow mesenchymal stromal cells and annulus fibrosus cells in repairing the degenerative discs of rabbits. Genet Mol Res. 2015; 14(1):2365-73.
44. Winkelstein BA, Allen KD, Setton LA. Intervertebral Disc Herniation: Pathophysiology and Emerging Therapies. The Intervertebral Disc. 2014; DOI 10.1007/978-3-7091-1535-0_19.
45. Henriksson HB, Svanvik T, Jonsson M , et al. Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model. Spine. 2009; 34:141–148.
46. Zhang Y, Drapeau S, Howard SA, et al. Transplantation of goat bone marrow stromal cells to the degenerating intervertebral disc in a goat disc injury model. Spine. 2011; 36:372–377.
PMid:20890267 PMCid:PMC3017738
47. Mizrahi O, Sheyn D, Tawackoli W, et al. Nucleus pulposus degeneration alters properties of resident progenitor cells. The Spine Journal. 2013; 13(7):803–814.
PMid:23578990 PMCid:PMC3759825
48. Gorensek M, Jaksimovic C, Kregar-Velikonja N. Nucleus pulposus repair with cultured autologous elastic cartilage derived chondrocytes. Cell. Mol. Biol. Lett. 2004; 9:363–373.
49. Kroeber MW, Unglaub F, Wang H, 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. 2002; 27:2684-2690.
50. Brinckerhoff CE, Martrisian LM. Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol. 2002; 3:207-214.
51. Moskowitz RW, Ziv I, Denko CW, et al. Spondylosis in sand rats: a model of intervertebral disc degeneration and hyperostosis. J Orthop Res. 1990; 8:401-411.
52. Bergknut N. Intervertebral Disc Degeneration in Dogs. Doctoral Thesis Swedish University of Agricultural Sciences Utrecht University Uppsala & Utrecht. 2011; p 111.
53. Hansen HJ. A pathologic-anatomical interpretation of disc degeneration in dogs. Acta Orthop Scand. 1951; 20:280-293.
54. Webb A. Potential sources of neck and back pain in clinical conditions of dogs and cats: a review. Vet J. 2003; 165(3):193 – 213.
55. Xin H, Zhang C, Wang D, et al. Tissue-engineered allograft intervertebral disc transplantation for the treatment of degenerative disc disease: experimental study in a beagle model. Tissue Eng Part A. 2013; 19(1-2):143-51.
56. Hohaus C, Ganey TM, Minkus Y, et al. Cell transplantation in lumbar spine disc degeneration disease. Eur Spine J. 2008; 17(4):492–503.
PMid:19005697 PMCid:PMC2587656
57. Lehmann TP, Filipiak K, Juzwa W, et al. Co‑culture of human nucleus pulposus cells with multipotent mesenchymal stromal cells from human bone marrow reveals formation of tunnelling nanotubes. Mol Med Rep. 2014; 9(2):574-82.
58. Strassburg S, Richardson SM, Freemont AJ, et al. Co-culture induces mesenchymal stem cell differentiation and modulation of the degenerate human nucleus pulposus cell phenotype. Regen Med. 2010; 5(5):701-11.
59. Richardson SM, Kalamegam G, Pushparaj PN, et al. Mesenchymal Stem Cells in Regenerative Medicine: Focus on Articular Cartilage and Intervertebral Disc Regeneration. A. Methods. 2015; S1046-2023(15):30091-8.
60. 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.
PMid:23369494 PMCid:PMC3612376
61. Zhang Z, Li F, Tian H, et al. Differentiation of adiposederived stem cells toward nucleus pulposus-like cells induced by hypoxia and a three-dimensional chitosanalginate gel scaffold in vitro. Chin Med J. 2014; 127:314-21.
62. Serigano K, Sakai D. Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. J Orthop Res. 2010; 28(10):1267-75.
63. Carragee E, Cuellar JM, Hurwitz EL, et al. Does provocative discography cause clinically important injury to the lumbar intervertebral disc? a ten-year matched cohort stud. Spine J. 2011; 11(10):S23–S24.
64. Adams MA, Dolan P, Hutton WC. The stages of disc degeneration as revealed by discograms. J Bone Joint Surg Br. 1986; 68(1):36–41.
65. Gruber HE, Rhyne AL, Hansen KJ, et al. Deleterious effects of discography radiocontrast solution on human annulus cell in vitro: changes in cell viability, proliferation, and apoptosis in exposed cells. Spine J. 2012; 12(4):329–335.
66. Martin JT, Gorth DJ, Beattie EE, et al. Needle puncture injury causes acute and long-term mechanical deficiency in a mouse model of intervertebral disc degeneration. J Orthop Res. 2013; 31(8):1276-82.
67. Le Maitre CL, Hoyland JA, Freemont AJ. Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression proile. Arthritis Res Ther. 2007; 9:77.
PMid:17688691 PMCid:PMC2206382
68. Park J-B, Chang H, Kim KW. Expression of Fas ligand and apoptosis of disc cells in herniated lumbar disc tissue. Spine. 2001; 26:618–621.
69. Brisby H, Papadimitriou N, Brantsing C, et al. The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: a descriptive study in humans. Stem Cells Dev. 2013; 22(5):804-14.
70. NOVOCART US National Library of Medicine. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/ NCT01640457 (2014).
71. Orozco L, Soler R, Morera C, et al. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation. 2011; 92(7):822-8.
72. Yoshikawa T, Ueda Y, Miyazaki K, et al. Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine. 2010; 35:E475–E480.
73. Hufe SMW, Mark AR. Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral disc. Stem cell dev. 2006; 15:136-137.
74. US National Library of Medicine. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/ NCT01860417 (2014).
75. US National Library of Medicine. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/ NCT01290367 (2014).
76. US National Library of Medicine. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/ NCT01771471 (2014).
77. Xie LW, Fang H, Chen AM, et al. 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.
78. Sun Z, Luo B, Liu Z-H, et al. Adipose-Derived Stromal Cells Protect Intervertebral Disc Cells in Compression: Implications for Stem Cell Regenerative Disc Therapy. Int J Biol Sci. 2015; 11(2):133–143.
PMid:25561896 PMCid:PMC4279089
79. Ganey T, Hutton CW, Moseley T, et al. Intervertebral Disc Repair Using Adipose Tissue-Derived Stem and Regenerative Cells Experiments in a Canine Model. Spine. 2009; 34(21):2297–2304.
80. US National Library of Medicine. ClinicalTrials.gov [online], https://clinicaltrials.gov/ct2/show/NCT02338271 (2015).

Ustymenko AM. Cell technologies in treatment of human intervertebral disc hernia: perspectives. Cell and Organ Transplantology. 2015; 3(2):202-207. doi: 10.22494/COT.V3I2.15


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