Mesenchymal Stem Cell-based Therapies Applied in Neurological Diseases

Background/Objectives: Neurodegenerative diseases (NDs) have a severe impact on patients’ quality of life, and effective treatments remain limited. As the focus is treating the symptoms, the root cause of the problem e commonly not addressed. Stem cells show an emerging potential due to the ability for self-renew combined with their ca-pability for differentiation into various cell lines, which makes them a strong candidate to regenerative therapies in general, and for application in neurological issues in par-ticular. This article provides an overview on the safety, efficacy and challenges associ-ated with the use of mesenchymal stem cells (MSCs), their derived secre-tome/exosomes and their combination with biomaterials in clinical and preclinical models of Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). Methods: A systematic search was conducted on PubMed, Web of Science and Scopus to identify published studies providing clinical and preclinical evidence on the use of MSCs in neurodegenerative disorders. Results: Overall, the literature consistently indicates that MSCs and their derivatives exert disease-modifying effects across multiple NDs. Across AD, PD, HD and ALS, preclinical studies uniformly report improvements in behavioural outcomes, attenuation of neuroinflammation, and neuroprotective effects, largely mediated by MSC paracrine signalling rather than direct cell replacement. Clinical studies to date consistently support the safety and feasibility of MSC-based therapies, while efficacy signals remain modest, heterogeneous and predominantly short-term, highlighting the need for larger, well-controlled trials. Conclusions: Inte-gration of genetic engineering, preconditioning, and EV technology may represent a paradigm shift in neuroregeneration, offering a scalable and minimally invasive fron-tier to improve long-term clinical outcomes in patients with AD, PD, HD, and ALS.