Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy.

An exceptional safety profile has been shown in a large number of cell therapy clinical trials that use mesenchymal stromal cells (MSCs). However, reliable potency assays are still lacking to predict MSC immunosuppressive efficacy in the clinical setting. Nevertheless, MSCs are approved in Japan and Europe for the treatment of graft-versus-host and Crohn's fistular diseases, but not in the United States for any clinical indication. We discuss potential mechanisms of action for the therapeutic effects of MSC transplantation, experimental models that dissect tissue modulating function of MSCs, and approaches for identifying MSC effects in vivo by integrating biomarkers of disease and MSC activity.