Therapy with mesenchymal stem cell transplantation in multiple sclerosis is ready for prime time: No.

Mark S Freedman Department of Medicine and The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada Mesenchymal stromal/stem cells (MSCs) have been extensively studied in the last two decades with the objective to promote tissue repair in many neurological diseases including multiple sclerosis (MS). Seminal studies demonstrated that MSC can promote remyelination,1 slow axonal degeneration, and modulate pathogenic immune response against myelin antigens2 in experimental autoimmune encephalomyelitis (EAE), a model of MS. MSC can be rather easily isolated from the bone marrow (BM) or adipose tissue and expanded in vitro with limited manipulation before intravenous (IV) or local administration in rodents but also in humans, thus providing a strong rationale for their use in MS.3 A consensus conference was held in 20104 to review all available data and concluded that it was time to prove the potential benefit of MSC by outlining the template for a proper randomized trial to examine for an in vivo biological effect of MSC to reduce inflammation and promote repair. Several small human clinical trials ensued and concluded universally that MSC administration to MS patients, regardless the route of administration, was safe and feasible and reported some effect on Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) metrics and might even reverse long-standing visual deficits.5 Despite these optimistic “hints,” the interpretation of results concerning efficacy of MSC on clinical and radiological parameters is, however, controversial:6 studies were vastly underpowered to generate consistent information on treatment effectiveness due to the limited number of patients and the heterogeneity of MS subtypes; furthermore, they were uncontrolled and unblinded, short-duration studies with limited extension of the clinical and radiological follow-up, rendering most results somewhat anecdotal, particularly for progressive MS patients. Other as yet unresolved issues make it difficult to compare results from these small studies, including the different sources for MSC isolation (e.g. BM, adipose tissue); dose https://doi.org/10.1177/13524585211062173 https://doi.org/10.1177/13524585211062173 Multiple Sclerosis Journal