REVIEW article
Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Mesenchymal Stem Cells and the Central Nervous System: Historical Perspectives and Future Directions
1. Feinberg School of Medicine, Northwestern University, Chicago, United States
2. Department of Neurological Surgery, Northwestern Medicine, 676 N St. Clair Street, Suite 2210, Chi-cago, IL 60611, USA, Chicago, United States
3. Simpson-Querrey Research Institute, 303 E Superior Street, Chicago, IL 60611, USA, Chicago, United States
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Abstract
Mesenchymal stem cells (MSCs) have been studied as a potential therapy for a wide range of conditions for approximately 30 years. MSCs have shown promise in treating pathologies of or affecting the central nervous system (CNS), specifically Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), traumatic brain injury (TBI), degenerative disc disease (DDD), and sepsis/meningitis. The therapeutic benefits of MSCs derive primarily from their arsenal of secreted factors that promote anti-inflammatory and pro-survival pathways while attenuating harmful immune responses, thus making them powerful immunomodulatory entities which are also capable of affecting a diverse range of cellular functions to promote endogenous mechanisms of repair. This review summarizes the current state of clinical trials research regarding pathologies of the CNS with a focus on historical progression and upcoming trials. We take a mechanistic approach to explain the therapeutic basis of MSCs and how this has informed clinical trials. We also mention the role of the MSC secretome and MSC exosomes in the treatment of CNS pathologies as well as their increasing use in clinical trials. Finally, we address the challenges inherent to the clinical translation and implementation of MSC therapies along with future directions of the field.
Summary
Keywords
Central Nervous System, clinical trials, Immunomodulation, Inflammation, mesenchymal stem cell, MSC secretome, neurodegeneration, Regenerative Medicine
Received
09 November 2025
Accepted
28 January 2026
Copyright
© 2026 Mazurek, Kaniuk and Ahuja. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Christopher Ahuja
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.