Adipose-derived stem cells: a pain relief treatment for intervertebral disc degeneration
Downloads
Intervertebral Disk Degeneration, or IVDD, refers to the natural process in which an intervertebral disk deteriorates (i.e., degenerates) over time-years and decades of life. It could result from the natural aging process or due to simple wear and tear. One of the most important components in spinal mechanics is the vertebral disc. It acts as a cushion between vertebral bodies connects them, and works as a shock-absorber during daily activities besides being the weight-bearing structure of vertebrae. IVDD is a major contributing factor to millions of lower back pain (LBP) sufferers worldwide. However, treatments to date are mostly pain-based (pain management: hitherto by surgical or non-surgical methods) and not disease-oriented due to a lack of understanding concerning the underlying mechanisms that trigger disc degeneration as reviewed in recent publications. While research has focused on reversing the degeneration process, adipose-derived stem cells (ADSCs) have shown promise as potential candidates because they are known to modulate immune responses and differentiate into multiple cell types making them an attractive prospect for regenerative therapy and a pain relief treatment. The present review article is intended to underscore the therapeutic features of ADSCs and their prospect in treating IVDD via innovative mechanisms, reviewing preclinical & clinical evidence along with future directions.
Downloads
1. Adams, M. A., & Roughley, P. J. (2006). What is intervertebral disc degeneration, and what causes it? Spine, 31(18), 2151-2161.
2. Aronowitz, J. A., Lockhart, R. A., & Hakakian, C. S. (2015). Mechanical versus enzymatic isolation of stromal vascular fraction cells from adipose tissue. Springerplus, 4, 1-9.
3. Comella, K., Silbert, R., & Parlo, M. (2017). Effects of the intradiscal implantation of stromal vascular fraction plus platelet rich plasma in patients with degenerative disc disease. Journal of translational medicine, 15, 1-8.
4. Dong, L., Li, X., Leng, W., Guo, Z., Cai, T., Ji, X., ... & Lin, J. (2023). Adipose stem cells in tissue regeneration and repair: From bench to bedside. Regenerative Therapy, 24, 547-560.
5. Figures created with https://www.biorender.com/.
6. Fodor, P. B., & Paulseth, S. G. (2016). Adipose derived stromal cell (ADSC) injections for pain management of osteoarthritis in the human knee joint. Aesthetic surgery journal, 36(2), 229-236.
7. Gimble, J. M., Katz, A. J., & Bunnell, B. A. (2007). Adipose-derived stem cells for regenerative medicine. Circulation research, 100(9), 1249-1260.
8. He, Y., Xia, J., Chen, H., Wang, L., Deng, C., & Lu, F. (2019). Human adipose liquid extract induces angiogenesis and adipogenesis: a novel cell-free therapeutic agent. Stem Cell Research & Therapy, 10, 1-14.
9. Jeong, J. H., Lee, J. H., Jin, E. S., Min, J. K., Jeon, S. R., & Choi, K. H. (2010). Regeneration of intervertebral discs in a rat disc degeneration model by implanted adipose-tissue-derived stromal
10. Jia, Q., Zhao, H., Wang, Y., Cen, Y., & Zhang, Z. (2023). Mechanisms and applications of adipose-derived stem cell-extracellular vesicles in the inflammation of wound healing. Frontiers in Immunology, 14, 1214757.
11. Kandi, V., & Vadakedath, S. (2022). Ethical considerations in clinical research: a comprehensive review. Am J Publ Health Res, 10, 42-52
12. Khazaei, S., Keshavarz, G., Bozorgi, A., Nazari, H., & Khazaei, M. (2022). Adipose tissue- derived stem cells: A comparative review on isolation, culture, and differentiation methods. Cell and tissue banking, 23(1), 1-16.
13. Kumar, H., Ha, D. H., Lee, E. J., Park, J. H., Shim, J. H., Ahn, T. K., ... & Han, I. B. (2017).
14. Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study. Stem cell research & therapy, 8, 1-14.
15. Lamblet, H., & Ferreira, L. M. (2022). Fat obtained from plastic surgery procedures—stem cells derived from adipose tissue and their potential in technological innovation: a narrative literature review and perspective on dissociative methods. European Journal of Plastic Surgery, 45(5), 701-731.
16. Liang, T., Li, P., Liang, A., Zhu, Y., Qiu, X., Qiu, J., ... & Gao, B. (2022). Identifying the key genes regulating mesenchymal stem cells chondrogenic differentiation: an in vitro study. BMC Musculoskeletal Disorders, 23(1), 985.
17. Lyons, G., Eisenstein, S. M., & Sweet, M. B. (1981). Biochemical changes in intervertebral disc degeneration. Biochimica et Biophysica Acta (BBA) - General Subjects, 673(4), 443-453.
18. Mazini, L., Ezzoubi, M., & Malka, G. (2021). Overview of current adipose-derived stem cell (ADSCs) processing involved in therapeutic advancements: flow chart and regulation updates before and after COVID-19. Stem cell research & therapy, 12(1), 1.
19. Mern, D. S., Walsen, T., Beierfuß, A., & Thomé, C. (2021). Animal models of regenerative medicine for biological treatment approaches of degenerative disc diseases.
20. Migliore, A., Sorbino, A., Bacciu, S., Bellelli, A., Frediani, B., Tormenta, S., ... & Foti, C. (2020). The technique of intradiscal injection: a narrative review. Therapeutics and clinical risk management, 953-968.
21. Mohammadian, M., Shamsasenjan, K., Nezhad, P. L., Talebi, M., Jahedi, M., Nickkhah, H., ... & Movassaghpour, A. (2013). Mesenchymal stem cells: New aspect in cell-based regenerative therapy. Advanced Pharmaceutical Bulletin, 3(2), 433-442.
22. Molinos, M., Almeida, C. R., Caldeira, J., Cunha, C., Gonçalves, R. M., & Barbosa, M. A. (2015). Inflammation in intervertebral disc degeneration and regeneration. Journal of the Royal Society Interface, 12(104), 20141191.
23. Munda, M., & Velnar, T. (2024). Stem cell therapy for degenerative disc disease: Bridging the gap between preclinical promise and clinical potential. Biomolecules and Biomedicine, 24(2), 210.
24. Qin, Y., Ge, G., Yang, P., Wang, L., Qiao, Y., Pan, G., ... & Geng, D. (2023). An Update on Adipose-Derived Stem Cells for Regenerative Medicine: Where Challenge Meets Opportunity. Advanced Science, 10(20), 2207334.
25. Risbud, M. V., & Shapiro, I. M. (2014). Role of cytokines in intervertebral disc degeneration: Pain and disc content. Nature Reviews Rheumatology, 10(1), 44-56.
26. Romaniyanto, F. N. U., Mahyudin, F., Prakoeswa, C. R. S., Notobroto, H. B., Tinduh, D., Ausrin, R., ... & Rhatomy, S. (2022). Adipose-Derived Stem Cells (ASCs) for Regeneration of Intervertebral Disc Degeneration. Stem Cells and Cloning: Advances and Applications, 67-76.
27. Roughley, P. J. (2004). Biology of intervertebral disc aging and degeneration: Involvement of the extracellular matrix. Spine, 29(23), 2691-2699.
28. Sakai, D., & Schol, J. (2017). Cell therapy for intervertebral disc repair: Clinical perspective.
journal of Orthopaedic Translation, 9, 8-18.
29. Sakai, D., Mochida, J., Iwashina, T., Watanabe, T., Nakai, T., Ando, K., & Hotta, T. (2005). Differentiation of mesenchymal stem cells transplanted to a rabbit degenerative disc model: Potential and limitations for stem cell therapy in disc regeneration. Spine, 30(21), 2379-2387.
30. Sclafani, A. P., Romo, T., & III, M. (2000). Injectable fillers for facial soft tissue enhancement. Facial plastic surgery, 16(01), 29-34.
31. Sheykhhasan, M., Wong, J. K., & Seifalian, A. M. (2019). Human adipose-derived stem cells with great therapeutic potential. Current stem cell research & therapy, 14(7), 532-548.
32. Skrypnyk, M. (2024). Current progress and limitations of research regarding the therapeutic use of adipose-derived stem cells: literature review. Journal of Umm Al-Qura University for Applied Sciences, 1-13.
33. Soufi, K. H., Castillo, J. A., Rogdriguez, F. Y., DeMesa, C. J., & Ebinu, J. O. (2023). Potential role for stem cell regenerative therapy as a treatment for degenerative disc disease and low back pain: a systematic review. International journal of molecular sciences, 24(10), 8893.
34. Stojanović, S., & Najman, S. (2019). The effect of conditioned media of stem cells derived from lipoma and adipose tissue on macrophages’ response and wound healing in indirect co-culture system in vitro. International journal of molecular sciences, 20(7), 1671.
35. Sun, Z., Luo, B., Liu, Z. H., Samartzis, D., Liu, Z., Gao, B., ... & Luo, Z. J. (2015). Adipose- derived stromal cells protect intervertebral disc cells in compression: implications for stem cell regenerative disc therapy. International journal of biological sciences, 11(2), 133.
36. Troell, R. J. (2014). Adipose-Derived Stem and Regenerative Cells: Harvesting, Processing, and Administration. In Stem Cells in Aesthetic Procedures: Art, Science, and Clinical Techniques (pp. 249-292). Berlin, Heidelberg: Springer Berlin Heidelberg.
37. Trzyna, A., & Banaś-Ząbczyk, A. (2021). Adipose-derived stem cells secretome and its potential application in “stem cell-free therapy”. Biomolecules, 11(6), 878.
38. Urban, J. P., & Roberts, S. (2003). Degeneration of the intervertebral disc. Arthritis Research & Therapy, 5(3), 120-130.
39. Kumar, S., Ashfaq, M. H., Ririe, A. K., Rusho, M. A., Hafeez, N., Agyapong, I. D., ... & Rafique, T. (2024). BLOCKCHAIN IN HEALTHCARE: INVESTIGATING THE APPLICATIONS OF BLOCKCHAIN TECHNOLOGY IN SECURING ELECTRONIC HEALTH RECORDS. A BIBLIOMETRIC REVIEW. Cuestiones de Fisioterapia, 53(03), 429-456.
40. Hussain, I., Ali, D. R., Bukhari, S. H., Kumar, S., Faraz, A. A., & Burki, S. (2025). AI-ENHANCED INTEGRATION OF MULTIMODAL DATA FOR EARLY PREDICTION OF HEART FAILURE EXACERBATIONS IN HIGH-RISK GROUPS. The Research of Medical Science Review. Zenodo. https://doi. org/10.5281/zenodo, 15181126.
41. Vergroesen, P. P., Kingma, I., Emanuel, K. S., Hoogendoorn, R. J., Welting, T. J., van Royen, B. J., van Dieën, J. H., & Smit, T. H. (2015). Mechanics and biology in intervertebral disc degeneration: A vicious circle. Osteoarthritis and Cartilage, 23(7), 1057-1070.
42. Vo, N. V., Hartman, R. A., Patil, P. R., & Brunger, J. M. (2016). Molecular mechanisms of biological aging in intervertebral discs. Journal of Orthopaedic Research, 34(8), 1289-1306.
43. Volarevic, V., Markovic, B. S., Gazdic, M., Volarevic, A., Jovicic, N., Arsenijevic, N., ... & Stojkovic, M. (2018). Ethical and safety issues of stem cell-based therapy. International journal of medical sciences, 15(1), 36.
44. Wang, Y., Che, M., & Xin, J. (2020). The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomedical Reports, 4(6), 741-746.
45. West, C. C., Murray, I. R., González, Z. N., Hindle, P., Hay, D. C., Stewart, K. J., & Péault, B. (2014). Ethical, legal and practical issues of establishing an adipose stem cell bank for research. Journal of Plastic, Reconstructive & Aesthetic Surgery, 67(6), 745-751.
46. Wu, A., March, L., Zheng, X., Huang, J., Wang, X., Zhao, J., ... & Hoy, D. (2020). Global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the Global Burden of Disease Study 2017. Annals of translational medicine, 8(6).
47. Wuertz, K., Vo, N., Kletsas, D., & Boos, N. (2012). Inflammatory and catabolic signalling in intervertebral discs: The roles of NF-kB and MAP kinases. European Cells and Materials, 23, 103-119.
48. Yuan, C., Song, W., Jiang, X., Wang, Y., Li, C., Yu, W., & He, Y. (2024). Adipose-derived stem cell-based optimization strategies for musculoskeletal regeneration: recent advances and perspectives. Stem Cell Research & Therapy, 15(1), 91.
49. Zhao, Y., Dong, H., Xia, Q., Wang, Y., Zhu, L., Hu, Z., ... & Xin, Z. (2024). A new strategy for intervertebral disc regeneration: The synergistic potential of mesenchymal stem cells and their extracellular vesicles with hydrogel scaffolds. Biomedicine & Pharmacotherapy, 172, 116238.
50. Zhang, J., Liu, Y., Chen, Y., Yuan, L., Liu, H., Wang, J., ... & Zhang, Y. (2020). Adipose-Derived stem cells: current applications and future directions in the regeneration of multiple tissues. Stem Cells International, 2020(1), 8810813.
51. Zhang, W., Sun, T., Li, Y., Yang, M., Zhao, Y., Liu, J., & Li, Z. (2022). Application of stem cells in the repair of intervertebral disc degeneration. Stem cell research & therapy, 13(1), 70.
52. Zielinska, N., Podgórski, M., Haładaj, R., Polguj, M., & Olewnik, Ł. (2021). Risk factors of intervertebral disc pathology—A point of view formerly and today—A review. Journal of clinical medicine, 10(3), 409.
Copyright (c) 2025 Dr Jeremy Pont, Prof. Pankaj Singh, Prof. Vivek Pratap Singh

This work is licensed under a Creative Commons Attribution 4.0 International License.