Tong Ming Liu, Wikie Tew, Zheng Yang, Bing Lim, James Hoi Po Hui, Eng Hin Lee, Yuin-Han Loh, Simon Cool. Understanding the molecular basis of mesenchymal stem cell stemness: implications for clinical applications. Cell Death Dis, 2025, 16(1):778. doi: 10.1038/s41419-025-08094-x
Abstract:
Human mesenchymal stem cells (MSCs) have been studied in over 1500 clinical trials to treat over 30 diseases. However, the
understanding towards MSC stemness remains under studied. So far, little is known about how MSCs maintain undifferentiated
state or commit to specific lineages under different microenvironmental cues. The lack of comprehensive understanding regarding
MSC stemness greatly hampers the translation of research findings into successful clinical application due to unclear mechanism of
action. Emerging evidence shows that a variety of genetic factors delicately regulate MSC self-renewal and differentiation. In this
review, we summarize the role of transcriptional factors, cell cycle regulators, genomic stability genes, cellular quality control,
epigenetic regulators, non-coding RNAs, mitochondrial function, growth factors and m6A modification in regulating the stemness
of MSCs. Strategies to maintain MSC stemness during ex-vivo expansion are also discussed. This review will deepen understanding
of MSC stemness for advancing clinical applications and provide insights into future directions for research aimed at improving
MSC-based therapies.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the Agency for Science, Technology and Research - Career Development Fund
Grant Reference no. : C210112047
This research / project is supported by the A*STAR - pre-gap funding
Grant Reference no. : I22D1AG050
This research / project is supported by the A*STAR - Industry Alignment Fund Pre-Positioning (IAF-PP)
Grant Reference no. : H18/01/a0/021 and H18/AH/a0/001
Description:
This is a post-peer-review, pre-copyedit version of an article published in Cell Death & Disease. The final authenticated version is available online at: http://dx.doi.org/10.1038/s41419-025-08094-x.