Intradiscal Mesenchymal Stromal/Stem Cell Therapy for Lumbar Discogenic Low Back Pain Due to Degenerative Disc Disease: A Systematic Review

Background Degenerative disc disease is a major contributor to chronic low back pain and disability worldwide. Conventional treatments, including physical therapy, pharmacologic management, and surgical interventions, often focus on symptom control rather than addressing the underlying biological degeneration of the intervertebral disc. Intradiscal mesenchymal stromal/stem cell therapy has emerged as a regenerative medicine approach aimed at modulating inflammation, restoring disc homeostasis, and improving clinical outcomes in patients with discogenic low back pain. Objective To evaluate the efficacy and safety of intradiscal mesenchymal stromal/stem cell therapy in adults with lumbar degenerative disc disease and discogenic low back pain. Methods A systematic review of human clinical studies was conducted following PRISMA guidelines. Eligible studies included randomized controlled trials, prospective controlled studies, and prospective single-arm interventional studies evaluating intradiscal administration of mesenchymal stromal/stem cells in adults with degenerative disc disease. Primary outcomes included pain reduction and functional improvement measured by validated scales such as the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI). Secondary outcomes included quality-of-life measures, imaging outcomes including magnetic resonance imaging findings and Pfirrmann disc degeneration grade where reported, reintervention rates, and safety outcomes including adverse events and malignancy reporting. Results Published clinical studies of intradiscal mesenchymal stromal/stem cell therapy consistently report reductions in pain scores and improvements in functional disability in patients with chronic discogenic low back pain. Across studies, patients receiving intradiscal MSC therapy demonstrated improvements in VAS pain scores and ODI functional scores over follow-up periods ranging from six months to three years. Safety reporting across studies has not identified consistent signals of severe treatment-related adverse events or malignancy. However, the available literature is limited by relatively small sample sizes, heterogeneity in cell sources and dosing strategies, and variability in study design. Conclusion Intradiscal mesenchymal stromal/stem cell therapy represents an emerging regenerative approach for the management of chronic discogenic low back pain associated with degenerative disc disease. Across the human clinical studies included in this systematic review, MSC therapy was consistently associated with improvements in patient-reported pain and functional disability, with generally favorable safety profiles reported during follow-up periods extending up to several years. While these findings suggest potential therapeutic benefit, the current evidence base remains limited by relatively small study populations, heterogeneity in cell sources and treatment protocols, and variability in outcome reporting. In addition, the relationship between clinical improvement and structural disc regeneration remains incompletely understood. Future clinical investigations should prioritize larger randomized controlled trials with standardized treatment methodologies, clearly defined patient selection criteria, and longer follow-up periods to better assess the durability and long-term safety of intradiscal MSC therapy. Continued research into the biological mechanisms underlying MSC-mediated effects within the intervertebral disc may also help refine regenerative treatment strategies and identify patient populations most likely to benefit from these therapies. Overall, the available clinical evidence suggests that intradiscal mesenchymal stromal/stem cell therapy may offer a promising biologically based treatment strategy for selected patients with degenerative disc disease and chronic discogenic low back pain. Further high-quality clinical trials will be essential to define the role of this therapy within the evolving landscape of regenerative spine medicine.