Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

Mesenchymal stem cells (MSCs) are broadly used in cell‐based regenerative medicine because of their self‐renewal and multilineage potencies in vitro and in vivo. To ensure sufficient amounts of MSCs for therapeutic purposes, cells are generally cultured in vitro for long‐term expansion or specific terminal differentiation until cell transplantation. Although physiologically up‐regulated reactive oxygen species (ROS) production is essential for maintenance of stem cell activities, abnormally high levels of ROS can harm MSCs both in vitro and in vivo. Overall, additional elucidation of the mechanisms by which physiological and pathological ROS are generated is necessary to better direct MSC fates and improve their therapeutic effects by controlling external ROS levels. In this review, we focus on the currently revealed ROS generation mechanisms and the regulatory routes for controlling their rates of proliferation, survival, senescence, apoptosis, and differentiation. A promising strategy in future regenerative medicine involves regulating ROS generation via various means to augment the therapeutic efficacy of MSCs, thus improving the prognosis of patients with terminal diseases.