Regulation Mechanisms and Maintenance Strategies of Stemness in Mesenchymal Stem Cells

Stemness pertains to the intrinsic ability of mesenchymal stem cells (MSCs) to undergo self-renewal and differentiate into multiple lineages, while simultaneously impeding their differentiation and preserving crucial differentiating genes in a state of quiescence and equilibrium. Owing to their favorable attributes, including uncomplicated isolation protocols, ethical compliance, and ease of procurement, MSCs have become a focal point of inquiry in the domains of regenerative medicine and tissue engineering. As age increases or ex vivo cultivation is prolonged, the functionality of MSCs decreases and their stemness gradually diminishes, thereby limiting their potential therapeutic applications. Despite the existence of several uncertainties surrounding the comprehension of MSC stemness, considerable advancements have been achieved in the clarification of the potential mechanisms that lead to stemness loss, as well as the associated strategies for stemness maintenance. This comprehensive review provides a systematic overview of the factors influencing the preservation of MSC stemness, the molecular mechanisms governing it, the strategies for its maintenance, and the therapeutic potential associated with stemness. Finally, we underscore the obstacles and prospective avenues in present investigations, providing innovative perspectives and opportunities for the preservation and therapeutic utilization of MSC stemness. Graphical Abstract