Young TSPC-Derived Exosomal circPVT1 Ameliorates Aging-Impaired Cell Function via SIRT1/NF-κB.
Weifeng HanDongqiang GuXiaoya LiHongguang ChenXu TaoLei ChenPublished in: Tissue engineering. Part C, Methods (2024)
Tendon stem/progenitor cell (TSPC) senescence is often associated with age-dependent tendon diseases and greatly reduces the capacities for tendon repair and replacement. Exosomes contain bioactive molecules and have been increasingly used in regenerative medicine. In the present study, we demonstrated the antiaging effects of young exosomes from circPVT1-overexpressing TSPCs at early passages (circPVT1-exo). These exosomes attenuated the phenotypes of aged TSPCs at late passages (L-TSPCs) by enhancing self-renewal and proliferation abilities, suppressing cell senescence, maintaining their tenogenic capacity, and weakening their osteogenic differentiation. Mechanistically, circPVT1-exo inhibited the NF-κB pathway and increased SIRT1 expression in L-TSPCs. Knockdown of SIRT1 reversed these effects as evidenced by increased senescence, decreased proliferation, and tenogenic differentiation. These results suggest that circPVT1-exo may ameliorate aging-impaired TSPC function by modulating the SIRT1/NF-κB pathway, suggesting that circPVT1-exo has therapeutic potential for age-related diseases.
Keyphrases
- signaling pathway
- mesenchymal stem cells
- oxidative stress
- dna damage
- pi k akt
- stem cells
- ischemia reperfusion injury
- lps induced
- endothelial cells
- anterior cruciate ligament reconstruction
- stress induced
- nuclear factor
- poor prognosis
- rotator cuff
- cell therapy
- bone marrow
- mouse model
- long non coding rna
- tissue engineering