Efficacy and safety of mesenchymal and haematopoietic stem cells in secondary progressive multiple sclerosis: a systematic review and meta-analysis
Authors: Shalhoub R 
Published: November 2023

Abstract

Introduction
Multiple sclerosis (MS) is a devastating, immune-mediated disease of the central nervous system (CNS)1. Despite extensive research, there is still no known definitive cure for MS1. Disease modifying therapies (DMTs) currently available are primarily approved for relapsing remitting multiple sclerosis (RRMS) and show limited evidence of efficacy in secondary progressive multiple sclerosis (SPMS). Moreover, DMTs do not halt disease progression or promote CNS repair2. In contrast, mesenchymal stem cells (MSCs) and haematopoietic stem cells (HSCs) have emerged as potential therapeutic approaches and have exhibited promising outcomes in MS clinical trials3.

Aim
The aim of this systematic review and meta-analysis was to assess the effectiveness and safety of MSCs and HSCs in the treatment of the SPMS sub-type.

Methods
A systematic search of PubMed, Web of Science, and Cochrane Library databases was conducted to identify eligible studies published from 1971 to 2022. Included studies focused specifically on SPMS and investigated MSC or HSC therapies. The systematic search identified 854 studies, following screening, fifteen studies (systematic review n = 15, meta-analysis n = 14) met the inclusion criteria, comprising 8 MSC studies and 7 HSC studies. The primary outcome measure was the expanded disability status scale (EDSS).
Ethics approval was not deemed necessary for this research, as it falls within the scope of systematic reviews and meta-analyses.

Results
The study revealed a significant difference between baseline and final follow-up disability scores (EDSS) in the included studies [random-effects, MD = -0.17, 95%CI (-0.28, -0.06), P = 0.002, I2 = 29%]. The experimental groups showed a significant improvement in EDSS scores compared to the control group [random-effects, MD = -0.38, 95%CI (-0.66, -0.09), P = 0.01, I2 = 59%]. No statistically significant difference in efficacy was observed between MSCs and HSCs (unequal variance t-test, P = 0.73). Moderate adverse events were predominantly associated with MSC studies, while HSC studies reported more hospitalizations and three deaths.

Discussion/Conclusion
MSC and HSC transplantation demonstrated efficacy in improving the clinical course of SPMS. MSCs were found to have a moderate safety profile, while HSCs raised concerns due to the higher incidence of hospitalizations and fatalities. Additional investigations are necessary to further consolidate and establish the safety profile of HSCs. Despite the positive outcomes observed in the clinical trials, larger and more rigorous randomized controlled trials (RCTs) are needed to draw definitive conclusions regarding the therapeutic efficacy of these therapies. The limited number of RCTs represents a significant limitation of this study.

References
1. Ghasemi N, Razavi S, Nikzad E. Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J. 2017; 19(1): 1-10.
2. Oliveira AG, Gonçalves M, Ferreira HM, Neves NM. Growing evidence supporting the use of mesenchymal stem cell therapies in multiple sclerosis: A systematic review. Stem Cell Res Ther. 2019; 10(1): 215.
3. Ardeshirylajimi A, Farshdousti Hagh M, Saki N, Mortaz E, Soleimani M, Rahim F. Feasibility of cell therapy in multiple sclerosis: A systematic review of 83 studies. Int J Hematol Oncol Stem Cell Res. 2013; 7(1): 13-30.