Podoplanin depletion in tonsil-derived mesenchymal stem cells induces cellular senescence via regulation of the p16Ink4a/Rb pathway

  • 0Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, Republic of Korea.

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Summary

This summary is machine-generated.

Podoplanin (PDPN) helps maintain stemness in tonsil-derived mesenchymal stem cells (TMSCs), reducing cellular senescence. PDPN levels decrease with passage, indicating its potential as a biomarker for MSC quality control in regenerative medicine.

Area Of Science

  • Regenerative Medicine
  • Stem Cell Biology
  • Cellular Senescence

Background

  • Mesenchymal stem cells (MSCs) are crucial for regenerative medicine but lose quality during in vitro expansion due to senescence.
  • Cellular heterogeneity and acquired senescence in expanded MSCs limit their therapeutic efficacy.
  • Investigating factors that maintain MSC stemness and mitigate senescence is critical for clinical applications.

Purpose Of The Study

  • To investigate the role of podoplanin (PDPN) in minimizing cellular senescence.
  • To determine if PDPN expression is associated with maintaining the stemness of tonsil-derived MSCs (TMSCs).
  • To evaluate PDPN as a potential biomarker for MSC quality.

Main Methods

  • Tonsil-derived MSCs (TMSCs) were isolated and cultured to early (3-7 passages) and late (>15 passages) stages.
  • Cellular senescence and MSC characteristics were assessed in relation to passage number.
  • PDPN expression was analyzed using fluorescence-activated cell sorting, and its function was studied using siRNA-mediated depletion.

Main Results

  • Late-passaged, senescent TMSCs showed reduced proliferation, telomere length, pluripotency marker expression, and differentiation potential.
  • PDPN protein levels decreased significantly with increased passage number.
  • PDPN-positive cells retained stemness markers and differentiation capacity, while PDPN depletion accelerated senescence via the p16Ink4a/Rb pathway.

Conclusions

  • PDPN expression is linked to the maintenance of stemness and reduced senescence in TMSCs.
  • PDPN levels decrease in a passage-dependent manner, correlating with cellular aging.
  • PDPN may serve as a valuable biomarker for assessing and mitigating cellular senescence in clinical MSC applications.

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