Biological approaches in degenerative disc disease. Where are we now?

  • Maria Korompilia Orthopaedic Department, School of Medicine, University of Ioannina, Ioannina, Greece
  • Ioannis Gkiatas Stavros Niarchos Foundation Complex Joint Reconstruction Center, Hospital for Special Surgery, New York, NY, USA
  • Dimitrios Gelalis School of Medicine, European University of Cyprus, Cyprus
  • Anastasios Korompilias Orthopaedic Department, School of Medicine, University of Ioannina, Ioannina, Greece
  • Emilios Pakos Orthopaedic Department, School of Medicine, University of Ioannina, Ioannina, Greece
  • Ioannis Gelalis Orthopaedic Department, School of Medicine, University of Ioannina, Ioannina, Greece
Keywords: intervertebral disc disease, biological therapies, tissue engineering

Abstract

Intervertebral disc (IVD) disease consists one of the main chronic- age related diseases mostly in patients over 60 years old. IVD degeneration is considered a multifactorial process with interaction of genetic, nutritional and environmental factors. Any nutritional and compositional imbalance leads to disturbance in biochemical and structural integrity.

Unfortunately common therapeutic methods- conservative and surgical- focus mainly on the patients and rather to the pathology of disc degeneration. Biological treatment strategies approach the condition at a molecular level and according with the stage of degeneration are classified into biomolecular therapy, cell therapy and tissue-engineering (TE) therapy.

During the first stage of the disease, where there is damage to biomolecules, biomoleucular therapy is suitable for promoting extracellular matrix (ECM) synthesis. This is achieved through injection of protein solutions (bone morphogenic proteins, osteogenic protein-1, transforming growth factor superfamily), platelet-rich-plasma and gene therapy injection (viral or non-viral vectors). In the midstage of disease, with cell amount reduction, cell therapy through mesenchymal stem cells and chondrocyte transplantation forms the best option for production- differentiation of ECM components and disc repair. Lastly, as degeneration reaches the final stage, implantation of TE disc-like constructs is considered the most optional reconstruction therapy for disc repair.

Biological therapeutic strategies in IVD disease consists a revolutionary method, address not to symptoms but to pathophysiology of the degeneration with purpose to improve population’s quality life

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References

1. Andersson GBJ, Bouchard J, Bozic KJ et al. 2008. The Burden of Musculoskeletal Diseases in the United States, 1st Edition (2008)
2. Vo NV, Hartman RA, Patil PR, et al. Molecular mechanisms of biological aging in intervertebral discs. J Orthop Res. 2016;34(8):1289-1306.
3. Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebral disc. Spine (Phila Pa 1976). 2004;29(23):2700-2709.
4. Dowdell, James et al. “Intervertebral Disk Degeneration and Repair.” Neurosurgery vol. 80,3S (2017): S46-S54. doi:10.1093/neuros/nyw078
5. Roughley PJ. Biology of intervertebral disc aging and degeneration: Involvement of the extracellular matrix. Spine (Phila Pa 1976) 2004 ;29:269122699.
6. Q. Yang, H.-W. Xu, S. Hurday, and B.-S. Xu, “Construction strategy and progress of whole intervertebral disc tissue en- gineering,” Orthopaedic Surgery, vol. 8, no. 1, pp. 11–18, 2016
7. An HS, Masuda K, Cs-Szabo G, et al. Biologic repair and regeneration of the intervertebral disk. J Am Acad Orthop Surg 2011;19(7):450–452
8. Yu Moriguchi, Marjan Alimi, Thamina Khair, George Manolarakis, Connor Berlin, Lawrence J. Bonassar, Roger Härtl, Biological Treatment Approaches for Degenerative Disk Disease: A Literature Review of In Vivo Animal and Clinical Data, Global Spine J, 2016;6:497-518
9. Vo NV, Hartman RA, Patil PR, et al. Molecular mechanisms of biological aging in intervertebral discs. J Orthop Res. 2016;34(8):1289-1306.
10. Chubinskaya S, Kawakami M, Rappoport L, Matsumoto T, Migita N, Rueger DC. Anti-catabolic effect of OP-1 in chronically compressed intervertebral discs. J Orthop Res 2007;25(4):517–530
11. Gruber HE, Fisher EC, Jr, Desai B, Stasky AA, Hoelscher G, Hanley EN., Jr Human intervertebral disc cells from the annulus: three-dimensional culture in agarose or alginate and responsiveness to TGF-beta1. Exp Cell Res. 1997;235:13–21.
12. Yoon TS, Su Kim K, Li J, Soo Park J, Akamaru T, Elmer WA, Hutton WC. The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro. Spine. 2003;28:1773–1780.
13. Wehling P (2002) Antiapoptotic and antidegenerative effect of an autologous IL-1ra/IGF-1/PDGF combination on human intervertebral disc cells in vivo. In: Proceeding of the international society for the study of the lumbar spine, 29th Annual Meeting,Cleveland, OH, p 24
14. An HS, Takegami K, Kamada H, et al. Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine (Phila Pa 1976). 2005;30(1):25-32
15. Wang, S., Chang, Q., Lu, J. et al. Growth factors and platelet-rich plasma: promising biological strategies for early intervertebral disc degeneration. International Orthopaedics (SICOT) 39, 927–934 (2015).
16. Navani A, Ambach MA, Wei JJ and Gupta D, Biologic Therapies for Intervertebral Degenerative Disc Disease: A Review of Novel Applications, J Stem Cells Res,Rev &Rep.2017; 4(1): 1023
17. Paglia DN, Singh H, Karukonda T, Drissi H, Moss IL. PDGF-BB Delays Degeneration of the Intervertebral Discs in a Rabbit Preclinical Model. Spine (Phila Pa 1976). 2016;41(8):E449-E458.
18. Akeda K, Imanishi T, Ohishi K, et al. Intradiscal injection of autologous serum isolated from platelet rich plasma for the treatment of discogenic low back pain: preliminary prospective clinical trial: GP141. Spine: Affiliated Society Meeting Abstracts 2011.
19. Cho H, Holt DC 3rd, Smith R, Kim SJ, Gardocki RJ, Hasty KA. The Effects of Platelet-Rich Plasma on Halting the Progression in Porcine Intervertebral Disc Degeneration. Artif Organs. 2016;40(2):190-195
20. Gelalis ID, Christoforou G, Charchanti A, et al. Autologous platelet-rich plasma (PRP) effect on intervertebral disc restoration: an experimental rabbit model. Eur J Orthop Surg Traumatol. 2019;29(3):545-551
21. Woods BI, Vo N, Sowa G, Kang JD. Gene therapy for intervertebral disk degeneration. Orthop Clin North Am. 2011;42(4):563-ix.
22. Ren XF, Diao ZZ, Xi YM, et al. Adeno-associated virus-mediated BMP-7 and SOX9 in vitro co-transfection of human degenerative intervertebral disc cells. Genet Mol Res. 2015;14(2):3736-3744. Published 2015 Apr 22.
23. Priyadarshani P, Li Y, Yao L. Advances in biological therapy for nucleus pulposus regeneration. Osteoarthritis Cartilage. 2016;24(2):206-212.
24. Leung VYL, Chan D, Cheung KMC. Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction. European Spine Journal. 2006;15(3):S406–S413
25. Longo UG, Papapietro N, Petrillo S, Franceschetti E, Maffulli N, Denaro V. Mesenchymal stem cell for prevention and management of intervertebral disc degeneration. Stem Cells Int. 2012;2012:921053.
26. Yoshikawa T, Ueda Y, Miyazaki K, Koizumi M, Takakura Y. Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine (Phila Pa 1976). 2010;35(11):E475-E480.
27. Pettine K, Suzuki R, Sand T, Murphy M. Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. Int Orthop. 2016;40(1):135-140
28. Hoogendoorn RJ, Lu ZF, Kroeze RJ, Bank RA, Wuisman PI, Helder MN. Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future. J Cell Mol Med. 2008;12(6A):2205-2216.
29. Sun Z, Luo B, Liu ZH, 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. Published 2015 Jan 1.
30. Rajpurohit R, Risbud MV, Ducheyne P, Vresilovic EJ, Shapiro IM. Phenotypic characteristics of the nucleus pulposus: expression of hypoxia inducing factor-1, glucose transporter-1 and MMP-2. Cell Tissue Res. 2002;308(3):401-407.
31. Ganey T, Libera J, Moos V, et al. Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine (Phila Pa 1976). 2003;28(23):2609-2620.
32. Langer R, Vacanti JP. Tissue engineering. Science. 1993;260:920–6.
33. Godwin J, Kuraitis D, Rosenthal N. Extracellular matrix considerations for scar-free repair and regeneration: insights from regenerative diversity among vertebrates. Int J Biochem Cell Biol. 2014;56:47-55.
34. Mizuno H, Roy AK, Vacanti CA, Kojima K, Ueda M, Bonassar LJ. Tissue-engineered composites of anulus fibrosus and nucleus pulposus for intervertebral disc replacement. Spine (Phila Pa 1976). 2004;29(12):1290-1298.
35. Moriguchi Y, Mojica-Santiago J, Grunert P, Pennicooke B, Berlin C, et al. (2017) Total disc replacement using tissue-engineered intervertebral discs in the canine cervical spine. PLOS ONE 12(10): e0185716.
Published
2021-04-26
Issue
Vol 72 No 1 (2021): Acta Orthopaedica Et Traumatologica Hellenica
Section
Basic Science

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