Stress-Induced Senescence of Human Umbilical Cord Mesenchymal Stromal Cells Caused by Mitomycin C.

Abstract

Studying stress-induced senescence of umbilical cord-derived mesenchymal stromal cells (UCMSCs) is important for ensuring the safety of their application in regenerative medicine. This study provides a comprehensive analysis of senescence features in UC-MSCs 7 days after treatment with mitomycin C (1.5 μg/mL). Despite the accumulation of DNA double-strand breaks (γH2AX/53BP1 foci) and complete proliferation arrest (the absence of Ki‑67⁺ cells and the loss of colony-forming ability) while maintaining viability, the cells did not acquire a classical senescent phenotype. Cell cycle arrest was mediated by activation of the p53/p21/p27 pathway without p16 involvement, and was accompanied by increased expression of SASP factors (IL‑8 and PAI‑1) and decreased levels of COL1A1 and SPARC, while SA-β-gal, oxidative stress, mitochondrial dysfunction, and lysosomal accumulation were absent. These findings indicate a unique response of UC-MSCs, namely, a p53-dependent proliferation arrest without full senescence, which reflects the high resistance of perinatal cells to aging.