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Understanding the molecular basis of mesenchymal stem cell stemness: implications for clinical applications

Tong Ming Liu1, Wikie Tew2, Zheng Yang3,4

  • 1Institute of Molecular and Cell Biology (IMCB), Agency for Science Technology and Research (A*STAR), Singapore, Singapore. dbsliutm@yahoo.com.

Cell Death & Disease
|November 3, 2025
PubMed

Insights

Human mesenchymal stem cells (MSCs) are crucial for treating diseases, but their stemness is poorly understood. This review details factors regulating MSC stemness and strategies for ex-vivo expansion to improve therapies.

Area of Science:

  • Stem Cell Biology
  • Regenerative Medicine

Background:

  • Human mesenchymal stem cells (MSCs) show therapeutic potential in over 1500 clinical trials for diverse diseases.
  • Understanding MSC stemness (self-renewal and differentiation potential) is critical but remains underdeveloped.
  • Lack of knowledge on MSC stemness mechanisms hinders clinical translation and effective application.

Purpose of the Study:

  • To comprehensively review factors regulating human mesenchymal stem cell (MSC) stemness.
  • To explore strategies for maintaining MSC stemness during ex-vivo expansion.
  • To provide insights for advancing MSC-based clinical therapies.

Main Methods:

  • Literature review summarizing current research on MSC stemness.
  • Analysis of genetic and molecular factors influencing MSC self-renewal and differentiation.
  • Discussion of ex-vivo expansion techniques for preserving MSC stemness.

Main Results:

  • Identified key regulators of MSC stemness including transcriptional factors, epigenetic modifiers, and non-coding RNAs.
  • Highlighted the roles of cell cycle, genomic stability, and mitochondrial function in maintaining stemness.
  • Discussed the impact of microenvironmental cues on MSC differentiation pathways.

Conclusions:

  • A deeper understanding of MSC stemness mechanisms is essential for successful clinical applications.
  • Strategies for maintaining stemness during ex-vivo expansion are crucial for therapeutic efficacy.
  • Further research into MSC stemness regulation will advance regenerative medicine and MSC-based therapies.

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