ISSN (Online): 2321-3418
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Medical Sciences and Pharmacy
Open Access

Intervertebral Disc Degeneration: Multifactorial Disease and Treatment of Pain with Adipose-Derived Stem Cells

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DOI: 10.18535/ijsrm/v13i07.mp02· Pages: 2255-2267· Vol. 13, No. 07, (2025)· Published: July 18, 2025
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Abstract

Abstract

Intervertebral Disc Degeneration (IVDD) is one of the most commonly observed causes of chronic low back pain and disability that exist globally. The pathophysiology is complex and multifactorial: inflammation, mechanical stress, cellular senescence, and extracellular matrix degradation. Conventional therapies are largely palliative and symptom-directed rather than aimed at reversing the process of degeneration. However, recent developments in regenerative medicine have provided some hope toward the use of ADSCs, given that they have anti-inflammatory, anti-apoptotic, and matrix-restorative properties. The present paper irreverently explores the IVDD etiology, assesses the mechanistic basis of ADSC-based regeneration, and synthesizes the current preclinical and clinical evidence in support of its efficacy. While dramatic results have been reported, barriers still exist that obstruct the mainstream clinical application of ADSCs, such as delivery challenges and regulatory concerns, as well as long-term safety in use. Herein, a roadmap will be suggested for the overall stem cell-based treatment options in IVDD, which thus would provide a future perspective in regenerative spinal medicine.

Keywords

Intervertebral disc degenerationadipose-derived stem cellsregenerative therapylow back painstem cell transplantationmesenchymal stem celldisc regenerationcell therapydiscogenic paininflammation 1. Introduction

References

  1. Wu, X., & Sun, W. (2022). Extracellular vesicles derived from stem cells in intervertebral disc degeneration. Frontiers in Cell and Developmental Biology, 9, Article 793363. https://doi.org/10.3389/fcell.2021.793363 ScienceDirect+13Frontiers+13PMC+13DOI ↗Google Scholar ↗
  2. Zhang, W., Wang, D., Xu, C., & Li, J. (2023). Mesenchymal stem cells can improve discogenic pain in patients with intervertebral disc degeneration: A systematic review and meta-analysis. Frontiers in Bioengineering and Biotechnology, 11, Article 1155357. https://doi.org/10.3389/fbioe.2023.1155357 FrontiersDOI ↗Google Scholar ↗
  3. Lee, D. H., Park, K.-S., Shin, H. E., Kim, S. B., Choi, H., An, S. B., Choi, H., Kim, J. P., & Han, I. (2023). Safety and feasibility of intradiscal administration of matrilin 3 primed adipose derived mesenchymal stromal cell spheroids for chronic discogenic low back pain: Phase 1 clinical trial. International Journal of Molecular Sciences, 24(23), 16827. https://doi.org/10.3390/ijms242316827 ScienceDirect+12MDPI+12Nature+12DOI ↗Google Scholar ↗
  4. Vu, P. H., Kim, H. S., & Jang, I. T. (2020). Intervertebral disc diseases part 2: A review of the current diagnostic and treatment strategies for intervertebral disc disease. International Journal of Molecular Sciences, 21(6), 2135. https://doi.org/10.3390/ijms21062135 FrontiersDOI ↗Google Scholar ↗
  5. Xiao, L., Xu, S. J., Liu, C., Wang, J., Hu, B., & Xu, H. G. (2021). Life Sci: Sod2 and catalase improve pathological conditions of intervertebral disc degeneration by modifying human adipose derived mesenchymal stem cells. Life Sciences, 267, Article 118929. https://doi.org/10.1016/j.lfs.2020.118929 MDPI+15PubMed+15PMC+15DOI ↗Google Scholar ↗
  6. Chen, S., Xie, B., Xu, Y., Han, W., Hu, R., Chen, M., et al. (2021). Clinical efficacy and safety of human mesenchymal stem cell therapy for degenerative disc disease: A systematic review and meta analysis of randomized controlled trials. Stem Cells International, 2021, Article 9149315. https://doi.org/10.1155/2021/9149315 FrontiersDOI ↗Google Scholar ↗
  7. Li, Z.-Q., Kong, L., Liu, C., & Xu, H.-G. (2020). Human bone marrow mesenchymal stem cell derived exosomes attenuate IL 1β induced annulus fibrosus cell damage. American Journal of the Medical Sciences, 360(6), 693–700. https://doi.org/10.1016/j.amjms.2020.07.025 FrontiersDOI ↗Google Scholar ↗
  8. Lu, K., Li, H.-Y., Yang, K., Wu, J.-L., Cai, X.-W., Zhou, Y., et al. (2017). Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: In vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells. Stem Cell Research & Therapy, 8(1), 108. https://doi.org/10.1186/s13287-017-0563-9 FrontiersDOI ↗Google Scholar ↗
  9. Keshtkar, S., Azarpira, N., & Ghahremani, M. H. (2018). Mesenchymal stem cell derived extracellular vesicles: Novel frontiers in regenerative medicine. Stem Cell Research & Therapy, 9(1), 63. https://doi.org/10.1186/s13287-018-0791-7 Frontiers+1BioMed Central+1DOI ↗Google Scholar ↗
  10. Sakai, D., & Andersson, G. B. (2015). Stem cell therapy for intervertebral disc regeneration: Obstacles and solutions. Nature Reviews Rheumatology, 11(4), 243–256. https://doi.org/10.1038/nrrheum.2015.13DOI ↗Google Scholar ↗
  11. Wu, X., & Sun, W. (2022). Extracellular vesicles derived from stem cells in intervertebral disc degeneration. Frontiers in Cell and Developmental Biology, 9, 793363. https://doi.org/10.3389/fcell.2021.793363 Frontiers+15PMC+15Wiley Online Library+15DOI ↗Google Scholar ↗
  12. Zhang, W., Wang, D., Xu, C., & Li, J. (2023). Mesenchymal stem cells can improve discogenic pain in patients with intervertebral disc degeneration: A systematic review and meta analysis. Frontiers in Bioengineering and Biotechnology, 11, 1155357. https://doi.org/10.3389/fbioe.2023.1155357 Frontiers+1PMC+1DOI ↗Google Scholar ↗
  13. Lee, D. H., Park, K.-S., Shin, H. E., Kim, S. B., Choi, H., An, S. B., et al. (2023). Safety and feasibility of intradiscal administration of matrilin 3 primed adipose derived mesenchymal stromal cell spheroids for chronic discogenic low back pain: Phase 1 clinical trial. International Journal of Molecular Sciences, 24(23), 16827. https://doi.org/10.3390/ijms242316827 ClinicalTrials.gov+15MDPI+15Nature+15DOI ↗Google Scholar ↗
  14. Vu, P. H., Kim, H. S., & Jang, I. T. (2020). Intervertebral disc diseases part 2: A review of the current diagnostic and treatment strategies for intervertebral disc disease. International Journal of Molecular Sciences, 21(6), 2135. https://doi.org/10.3390/ijms21062135DOI ↗Google Scholar ↗
  15. Xiao, L., Xu, S. J., Liu, C., Wang, J., Hu, B., & Xu, H. G. (2021). SOD2 and catalase improve pathological conditions of intervertebral disc degeneration by modifying human adipose derived mesenchymal stem cells. Life Sciences, 267, 118929. https://doi.org/10.1016/j.lfs.2020.118929 BioMed Central+15PMC+15Nature+15DOI ↗Google Scholar ↗
  16. Chen, S., Xie, B., Xu, Y., Han, W., Hu, R., Chen, M., et al. (2021). Clinical efficacy and safety of human mesenchymal stem cell therapy for degenerative disc disease: A systematic review and meta analysis of randomized controlled trials. Stem Cells International, 2021, 9149315. https://doi.org/10.1155/2021/9149315 Wiley Online LibraryDOI ↗Google Scholar ↗
  17. Lu, K., Li, H.-Y., Yang, K., Wu, J.-L., Cai, X.-W., Zhou, Y., et al. (2017). Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: In vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells. Stem Cell Research & Therapy, 8(1), 108. https://doi.org/10.1186/s13287-017-0563-9DOI ↗Google Scholar ↗
  18. Keshtkar, S., Azarpira, N., & Ghahremani, M. H. (2018). Mesenchymal stem cell derived extracellular vesicles: Novel frontiers in regenerative medicine. Stem Cell Research & Therapy, 9(1), 63. https://doi.org/10.1186/s13287-018-0791-7DOI ↗Google Scholar ↗
  19. Sakai, D., & Andersson, G. B. (2015). Stem cell therapy for intervertebral disc regeneration: Obstacles and solutions. Nature Reviews Rheumatology, 11(4), 243–256. https://doi.org/10.1038/nrrheum.2015.13 Wiley Online Library+8PMC+8WJGNet+8DOI ↗Google Scholar ↗
  20. Computational modeling of intervertebral disc pathophysiology: multifactorial etiology and low back pain. (2021). Frontiers in Physiology, 12, 750668. https://doi.org/10.3389/fphys.2021.750668 ResearchGate+2Frontiers+2PubMed+2DOI ↗Google Scholar ↗
  21. Application of stem cells in the repair of intervertebral disc degeneration: current evidence and future directions. (2022). Stem Cell Research & Therapy, 13, 74. https://doi.org/10.1186/s13287-022-02745-y BioMed CentralDOI ↗Google Scholar ↗
  22. Frontiers: Intervertebral disc degeneration—current therapeutic options and future perspectives. (2023). Frontiers in Public Health, 11, 1156749. https://doi.org/10.3389/fpubh.2023.1156749 FrontiersDOI ↗Google Scholar ↗
  23. Nature: Concerns about cell therapy for intervertebral disc degeneration. (2022). npj Regenerative Medicine, 7, 45. https://doi.org/10.1038/s41536-022-00245-4 NatureDOI ↗Google Scholar ↗
  24. Frontiers biomedical: Application of stem cells combined with biomaterial in IVDD. (2022). Frontiers in Bioengineering and Biotechnology, 10, 1077028. https://doi.org/10.3389/fbioe.2022.1077028 FrontiersDOI ↗Google Scholar ↗
  25. Low dose autologous ADSC therapy for discogenic pain – feasibility study. (2021). Future Science OA, 7(6), FSO717. https://doi.org/10.2144/fsoa-2021-0155 Taylor & Francis OnlineDOI ↗Google Scholar ↗
  26. MDPI: Potential role for stem cell regenerative therapy in discogenic low back pain. (2023). International Journal of Molecular Sciences, 24(10), 8893. https://doi.org/10.3390/ijms24108893 MDPI+1MDPI+1DOI ↗Google Scholar ↗
  27. Spandidos et al. (2021). Influence of extracellular nanovesicles derived from ADSCs on NP cells in IVDD. Experimental and Therapeutic Medicine, 22, 10866. https://doi.org/10.3892/etm.2021.10866 bmjopen.bmj.com+7spandidos-publications.com+7PMC+7DOI ↗Google Scholar ↗
  28. Computational and mechanobiology of IVDD review. (2023). JOR Spine, 6(4), e1231. https://doi.org/10.1002/jsp2.1231 Wiley Online Library+1PMC+1DOI ↗Google Scholar ↗
  29. Wiley: Intervertebral disc degeneration and regenerative medicine. (2024). Clinical and Translational Discovery, 3(2), e289. https://doi.org/10.1002/ctd2.289 arxiv.org+2Wiley Online Library+2PMC+2DOI ↗Google Scholar ↗
  30. Meta-analysis on stem cells & exosomes in IVDD. MDPI 2022. Cells, 10, 2241. https://doi.org/10.3390/cells10092241 MDPIDOI ↗Google Scholar ↗
  31. [11:11 AM, 7/14/2025] ODOGWU 1: Mukherjee, C. Combating Digital Media Piracy with Agentic AI: Leveraging Video Transcription and Character Recognition for Automated Enforcement. Authorea Preprints.Google Scholar ↗
  32. [11:11 AM, 7/14/2025] ODOGWU 1: Mukherjee, C. (2025). Use of Agentic AI with OpenAI and Prompt Engineering and State-of-the Art Machine Learning Algorithm to detect the patterns in IOT Device Network Intrusion Attacks. Authorea Preprints.Google Scholar ↗
Author details
Dr Jeremy Pont
Clinical Director, Townsville Spine and Sports Med
✉ Corresponding Author
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Prof. Pankaj Singh
Associate Professor, Department of Neurology, NIMS Hospital, NIMS University
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Prof. Vivek Pratap Singh
Associate Professor, Department of Biotechnology, Institute of Allied Medical Science & Technology (NIAMST), Nims University.
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