New insights on translational development of mesenchymal stromal cells for suppressor therapy

The discovery of the immunosuppressive properties of mesenchymal stromal cells (MSCs) has given new hope to patients suffering from autoimmune diseases as their lack of immunogenicity in addition to their immunosuppressive and regenerative properties makes them an ideal biological agent for the treatment of various disorders ranging from autoimmune diseases to tissue injury. The translational promises of a safer and more effective therapy has however suffered a setback with the recent release of the results from Phase III randomized clinical trial using MSCs for treatment of steroid refractory acute graft-versus-host disease (GvHD), which failed to meet its primary efficacy endpoint. In this review, we will address the current knowledge of the immunosuppressive mechanisms of MSCs from in vitro studies to animal models and then look upon the results obtained from human clinical trials in order to provide failure analysis of negative studies. We will conclude by proposing future directions which could help address this issue and allow rational development of MSCs as an effective and useful cell-based immunotherapeutic.