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 invitro self-renewal ability, and can be readily engineered to enhance their immunomodulatory functions. 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 communicated via MSC-secreted cytokines; however, apoptotic and metabolically inactivated MSCs have more recently been shown to possess immunomodulatory potential, in which regulatory T cells and monocytes play a key role. We review the immunomodulatory aspects of naïve and engineered MSCs, and discuss strategies for increasing the potential of successfully using MSCs in clinical settings. MSCs are multipotent cells that are emerging as the most promising means of allogeneic cell therapy.MSCs participate in both innate and adaptive immunity, and their immunomodulatory functions are exerted mainly via interactions with immune cells through cell-to-cell contact and paracrine activity.Engineering MSCs to express specific immunomodulatory agents contributes to MSC capacity and pluripotency, and also enables them to deliver large doses of cancer-targeting biologics with a single dose.MSC administration has shown potential efficacy in the treatment of several diseases that resist standard treatment. However, there are some challenges in efficiently translating MSC-based therapeutics into the clinic.Efficient homing and migration of MSCs to the target tissue will be essential for the future development of MSC-based therapies.