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Mesenchymal stem cells (MSCs) have emerged as a promising regenerative approach due to their capacity for differentiation, immunomodulation, and secretion of bioactive factors that promote tissue repair. This review summarises findings from experimental and clinical studies investigating the therapeutic potential of MSC-based therapies for intervertebral disc regeneration, with particular focus on translational challenges that limit their clinical application. Preclinical studies generally show that MSC implantation can enhance extracellular matrix production, improve disc hydration, and modulate inflammatory processes within degenerated discs. Early clinical trials report improvements in pain and functional outcomes; however, consistent structural regeneration has not been reliably demonstrated. The limited clinical translation of MSC therapy is associated with several key challenges, including poor cell survival in the harsh disc microenvironment, variability in cell sources and manufacturing protocols, inadequate cell retention following intradiscal injection, and a lack of standardised outcome measures. In addition, regulatory and manufacturing barriers further complicate the development of reproducible and scalable MSC-based therapies. Although MSC-based therapies represent a promising strategy for the biological treatment of intervertebral disc degeneration, further research is required to improve cell survival, optimise delivery systems, standardise manufacturing procedures, and conduct large-scale controlled clinical trials to establish long-term safety and efficacy. Addressing these translational barriers will be essential for the successful integration of MSC-based therapies into clinical practice.<\/jats:p>","DOI":"10.3390\/bioengineering13050544","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:07:26Z","timestamp":1779206846000},"page":"544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Bench to Bedside: Translational Barriers in Mesenchymal Stem Cell Therapy for Intervertebral Disc Degeneration"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3492-0297","authenticated-orcid":false,"given":"Lidija","family":"Gradisnik","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences, Medical Faculty of Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borut","family":"Prestor","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-3786","authenticated-orcid":false,"given":"Uros","family":"Maver","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Medical Faculty of Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6283-4348","authenticated-orcid":false,"given":"Tomaz","family":"Velnar","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Alma Mater Europaea University Maribor, 2000 Maribor, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.4252\/wjsc.v7.i1.186","article-title":"Stem cells for spine surgery","volume":"7","author":"Schroeder","year":"2015","journal-title":"World J. 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