# Mesenchymal Stem Cell-Based Therapies Applied in Neurological Diseases: A Systematic Review

## TL;DR

This paper reviews how mesenchymal stem cells may help treat neurological diseases like Alzheimer's and Parkinson's by reducing inflammation and protecting brain cells.

## Contribution

The paper systematically reviews the safety, efficacy, and challenges of mesenchymal stem cell therapies in multiple neurodegenerative diseases.

## Key findings

- MSCs and their secretome show disease-modifying effects in Alzheimer's, Parkinson's, Huntington's, and ALS.
- Preclinical studies show MSCs improve behavior and reduce neuroinflammation via paracrine signaling.
- Clinical trials confirm safety but show modest and short-term efficacy, calling for larger trials.

## Abstract

Background/Objectives: Neurodegenerative diseases (NDs) have a severe impact on patients’ quality of life, and effective treatments remain limited. As the focus is on treating the symptoms, the root cause of the problem is commonly not addressed. Mesenchymal stem cells show an emerging potential due to the ability for self-renewal combined with their capability for differentiation into various cell lines, which makes them a strong candidate for regenerative therapies in general, and for application in neurological issues in particular. This article provides an overview of the safety, efficacy, and challenges associated with the use of mesenchymal stem cells (MSCs) and their derived secretome in clinical and preclinical models of Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). Methods: A systematic search was conducted on PubMed 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 MSCs’ 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: Integration of genetic engineering, preconditioning, and EV technology may represent an emerging therapeutic approach that may complement existing neuroregeneration treatments, offering a scalable and minimally invasive frontier to improve long-term clinical outcomes in patients with AD, PD, HD, and ALS.