Understanding the Molecular Basis of Mesenchymal Stem Cell Stemness: Implications for Clinical Applications

This review highlights the current understanding of the molecular basis of mesenchymal stem cell (MSC) stemness, which is crucial for their clinical application in treating over 30 diseases, as evidenced by over 1500 clinical trials. Despite their potential, the mechanisms by which MSCs maintain their undifferentiated state or differentiate in response to environmental cues remain poorly understood, hindering clinical translation. The review discusses the roles of various genetic and epigenetic factors, including transcriptional factors, cell cycle regulators, and non-coding RNAs, in regulating MSC stemness. It also explores strategies for maintaining MSC stemness during ex-vivo expansion, aiming to enhance the effectiveness of MSC-based therapies and guide future research directions.