A consensus statement addressing mesenchymal stem cell transplantation for multiple sclerosis: it's time!

ABSTRACT

Multiple sclerosis is a neurodegenerative disease of the central nervous system that is characterized by inflammation, demyelination with associated accumulation of myelin debris, oligodendrocyte and axonal loss. Current therapeutic interventions for multiple sclerosis predominantly modulate the immune system and reduce the inflammatory insult by general, non-specific mechanisms but have little effect on the neurodegenerative component of the disease. Predictably, the overall long-term impact of treatment is limited since the neurodegenerative component of the disease, which can be the dominant process in some patients, determines permanent disability. Mesenchymal stem cells, which are endowed with potent immune regulatory and neuroprotective properties, have recently emerged as promising cellular vehicles for the treatment of MS. Preclinical evaluation in experimental models of MS have shown that MSCs are efficacious in suppressing clinical disease. Mechanisms that may underlie these effects predominantly involve the secretion of immunomodulatory and neurotrophic growth factors, which collectively act to limit CNS inflammation, stimulate neurogenesis, protect axons and promote remyelination. As a logical progression to clinical utility, the safety of these cells have been initially assessed in hematological, cardiac and inflammatory diseases. Importantly, transplantation with autologous or allogeneic MSCs has been well tolerated by patients with few significant adverse effects. On the basis of these results, new, multicentre clinical trials have been launched to assess the safety and efficacy of MSCs for inflammatory MS. It thus comes as no surprise that the coalescence of an international group of experts have convened to generate a consensus guide for the transplantation of autologous bone marrow-derived MSC which, in time, may set the foundation for the next generation of therapies for the treatment of MS patients.