Autologous and allogeneic hematopoietic stem cell transplantation for Multiple Sclerosis: perspective on mechanisms of action.
Multiple Sclerosis (MS) is a frequent demyelinating immune-mediated disease of the central nervous system (CNS) that affects principally young adults and leads to severe physical and cognitive impairment. The current standard treatment makes use of the immune modulators beta-interferon, glatiramer acetate and natalizumab, or immunosuppressants such as mitoxantrone. However, these agents are only partially effective and in a number of patients fail to achieve satisfactory disease control. Autologous hematopoietic stem cell transplantation (HSCT) is being explored in the treatment of severe MS as a means of delivering high-dose immunosuppression followed by 'rescue' of the immuno-hematopoietic system with autologous HSC. The potential therapeutic benefit is based on the concept of so-called 'resetting' the immune system. The use of allogeneic HSCT as a possible therapeutic approach for severe MS is inspired by case reports of MS patients that underwent allogeneic HSCT for a concomitant hematological malignancy, and subsequently is supported by data from rodent models of MS. Allogeneic HSCT may offer specific therapeutic effects, such as the replacement of the autoreactive immune compartment by healthy allogeneic cells and the development of a graft-versus-autoimmunity (GVA) effect. Here, we review the currently available experimental and clinical evidence to support the role of autologous and allogeneic HSCT in MS.
Van Wijmeersch
Bart
B
Laboratory of Experimental Transplantation, University of Leuven, Belgium.
Sprangers
Ben
B
Dubois
Bénédicte
B
Waer
Mark
M
Billiau
An D
AD
D000818:Animals; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D009103:Multiple Sclerosis / Q000601:surgery*; D014182:Transplantation, Autologous / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*