Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential

Mesenchymal stem/stromal cells (MSCs) are multipotent cells that are emerging as the most promising means of allogeneic cell therapy. MSCs have inherent immunomodulatory characteristics, trophic activity, high in vitro self-renewal ability, and can be readily engineered to enhance their immunomodulatory func-tions. MSCs affect the functions of most immune effector cells via direct contact with immune cells and local microenvironmental factors. Previous studies have confirmed that the immunomodulatory effects of MSCs are mainly communi-cated via MSC-secreted cytokines; however, apoptotic and metabolically inactivated MSCs have more recently been shown to possess immunomodula-tory potential, in which regulatory T cells and monocytes play a key role. We review the immunomodulatory aspects of naive and engineered MSCs, and discuss strategies for increasing the potential of successfully using MSCs in clinical settings.