Bridging the Gap Between Experimental and Clinical Applications of Mesenchymal Stromal Cell Therapy in Intervertebral...

Intervertebral disc (IVD) degeneration is a major cause of chronic low back pain and disability worldwide. Although current treatment strategies effectively alleviate symptoms, they do not restore disc structure or reverse the underlying biological processes responsible for degeneration. Mesenchymal stromal cell (MSC)-based therapies have emerged as promising regenerative approaches owing to their immunomodulatory, anti-inflammatory, and extracellular matrix-regenerative properties, mediated predominantly through paracrine signalling rather than long-term cellular engraftment. Despite encouraging preclinical results, clinical translation remains limited by poor cell survival within the hostile disc microenvironment, protocol heterogeneity, and insufficient long-term clinical evidence. This review critically examines the current state of MSC-based therapy for IVD degeneration by integrating experimental findings, clinical evidence, and emerging translational strategies. Particular emphasis is placed on the biological mechanisms of MSC-mediated regeneration, comparison of different MSC sources, advances in extracellular vesicle- and exosome-based cell-free therapies, and the growing role of quantitative magnetic resonance imaging, molecular biomarkers, and precision diagnostics in patient selection and treatment monitoring. In addition, the review discusses the major biological, technical, manufacturing, and regulatory challenges that currently limit clinical implementation. Collectively, the evidence indicates that successful translation of MSC-based therapies will require not only optimised cell products but also standardised manufacturing, biomaterial-assisted delivery systems, advanced diagnostic biomarkers, and well-designed multicentre clinical trials. Integrating these advances will be essential for transforming MSC-based therapies into safe, standardised, and disease-modifying treatments for patients with intervertebral disc degeneration.