Mesenchymal stem cells for multiple sclerosis: hype or hope?

In the search for new approaches to treat or even cure multiple sclerosis, several forms of cell-based therapies have been explored, including haematopoietic stem cells, mesenchymal stem cells, and oligodendrocyte progenitor cells. 1 Scolding NJ Pasquini M Reingold SC Cohen JA on behalf of attendees at the International Conference on Cell-Based Therapies for Multiple SclerosisCell-based therapeutic strategies for multiple sclerosis. Brain. 2017; 140: 2776-2796 Crossref PubMed Scopus (110) Google Scholar In the past 15 years, several small uncontrolled trials have assessed the safety and feasibility of approaches using mesenchymal stem cells derived from diverse tissues (eg, bone marrow, adipose tissue, or placenta), with different routes of administration (eg, intravenous or intrathecal), and various outcome measures (eg, clinical, neurophysiological, or MRI-based measures). 1 Scolding NJ Pasquini M Reingold SC Cohen JA on behalf of attendees at the International Conference on Cell-Based Therapies for Multiple SclerosisCell-based therapeutic strategies for multiple sclerosis. Brain. 2017; 140: 2776-2796 Crossref PubMed Scopus (110) Google Scholar Petrou and colleagues 2 Petrou P Kassis I Levin N et al. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis. Brain. 2020; 143: 3574-3588 Crossref PubMed Scopus (48) Google Scholar did a randomised, double-blind, placebo-controlled trial to investigate the safety and efficacy of bone marrow-derived mesenchymal stem cells in patients with progressive multiple sclerosis. Following a complex crossover design, 48 patients with secondary progressive (n=41) or primary progressive (n=7) multiple sclerosis received mesenchymal stem cells or placebo via intravenous or intrathecal injection. The results were positive in that the primary efficacy outcome based on the Expanded Disability Status Scale was met. 2 Petrou P Kassis I Levin N et al. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis. Brain. 2020; 143: 3574-3588 Crossref PubMed Scopus (48) Google Scholar Significantly fewer patients had treatment failure in the groups treated with mesenchymal stem cells intrathecally (6·7%) or intravenously (9·7%) than those in the sham-treated group (41·9%; p=0·0003 vs intrathecal administration; p=0·0008 vs intravenous administration). 2 Petrou P Kassis I Levin N et al. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis. Brain. 2020; 143: 3574-3588 Crossref PubMed Scopus (48) Google Scholar Patients with MRI activity and those who received mesenchymal stem cells intrathecally showed the largest benefit. 2 Petrou P Kassis I Levin N et al. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis. Brain. 2020; 143: 3574-3588 Crossref PubMed Scopus (48) Google Scholar Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomised, double-blind crossover trialBone marrow-derived MSC treatment was safe and well tolerated but did not show an effect on GELs, an MRI surrogate marker of acute inflammation, in patients with active forms of multiple sclerosis, at week 24. Thus, this study does not support the use of bone marrow-derived MSCs to treat active multiple sclerosis. Further studies should address the effect of MSCs on parameters related to tissue repair. Full-Text PDF