Treatment of Graft-Versus-Host Disease Using Allogeneic Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) have attracted significant attention recently because of their immunomodulatory function. Due to their immunosuppressive role, MSCs have been suggested as a novel medical therapeutic option to treat graft-versus-host disease (GVHD) and autoimmune diseases. Severe GVHD is a lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). However, there have been only a few limited therapeutic options for the treatment of GVHD. Since the initial studies and use of MSCs, density-gradient centrifugation-based isolation has been the primary conventional protocol for the isolation of clinical trial grade nonclonal MSCs in the treatment of severe GVHD and other diseases. Recently, clonal MSCs isolated by the subfractionation culturing method (SCM) have been also used in a clinical setting to treat severe GVHD. Although there are concerns about the immunogenicity of allogeneic MSCs, all the clinical trials using allogeneic nonclonal and clonal MSCs performed in the last decade have shown that no significant adverse effects or ectopic transformation were involved with allogeneic MSCs. This suggests that allogeneic MSCs can be a promising therapeutic option for the treatment of steroid- refractory acute GVHD. However, further investigations are needed to understand the exact mechanisms of the functions of MSCs and larger, well-designed human clinical trials are necessary to confirm the long-term safety and efficacy of MSCs for the treatment of GVHD and other autoimmune diseases.