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Young TSPC-Derived Exosomal circPVT1 Ameliorates Aging-Impaired Cell Function via SIRT1/NF-κB

Weifeng Han1, Dongqiang Gu2, Xiaoya Li2

  • 1Department of Orthopaedics, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Tissue Engineering. Part C, Methods
|June 6, 2024
PubMed

Insights

Young exosomes from modified tendon stem cells can reverse aging in aged cells. This discovery offers potential therapeutic strategies for age-related tendon diseases and enhances regenerative medicine approaches.

Area of Science:

  • Regenerative Medicine
  • Cellular Senescence
  • Biomolecular Signaling

Background:

  • Tendon stem/progenitor cell (TSPC) senescence contributes to age-related tendon diseases, impairing repair and regeneration.
  • Exosomes, vesicles carrying bioactive molecules, are promising tools in regenerative medicine.

Purpose of the Study:

  • To investigate the antiaging effects of exosomes derived from circPVT1-overexpressing TSPCs (circPVT1-exo) on aged TSPCs.
  • To elucidate the underlying molecular mechanisms of circPVT1-exo in ameliorating TSPC aging.

Main Methods:

  • Isolation and characterization of circPVT1-exo from early-passage TSPCs.
  • Treatment of late-passage TSPCs (L-TSPCs) with circPVT1-exo.
  • Assessment of TSPC self-renewal, proliferation, senescence, tenogenic, and osteogenic capacities.
  • Investigation of the SIRT1/NF-κB signaling pathway.

Main Results:

  • circPVT1-exo attenuated L-TSPC senescence, enhancing self-renewal, proliferation, and tenogenic capacity while suppressing osteogenic differentiation.
  • circPVT1-exo inhibited the NF-κB pathway and upregulated SIRT1 expression in L-TSPCs.
  • SIRT1 knockdown reversed the beneficial effects of circPVT1-exo, confirming its crucial role.

Conclusions:

  • circPVT1-exo demonstrates significant antiaging effects on aged TSPCs.
  • The therapeutic potential of circPVT1-exo in age-related tendon diseases is linked to its modulation of the SIRT1/NF-κB pathway.
Keywords:
NF-κBSIRT1circPVT1senescencetendon stem/progenitor cell

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