Vitronectin Mediates Survival of Human WJ-MSCs Under Inflammatory Temperature Stress Via Cell Cycle Arrest

BACKGROUND: Due to their anti-inflammatory and immunomodulatory capabilities, mesenchymal stem cells (MSCs) are being widely used in cell-based therapies for the treatment of a wide spectrum inflammatory disorders. Despite promises, substantial cell loss post transplantation leads compromised therapeutic benefits clinical trials, which remains challenge overcome. Inflammatory microenvironment comprises presence pro-inflammatory cytokines, elevated temperature, etc., could hamper MSC viability following transplantation. Thus, identifying underlying molecular factors controlling survival mechanism under such stress conditions becomes important. Also, since MSCs from different origins have significantly varied biology, choosing appropriate source be critical determining fate transplanted stressful milieu. OBJECTIVE: As extracellular matrix (ECM) components can mediate signals, present study, we evaluated role ECM matricellular protein, vitronectin (VTN), human umbilical cord-derived Wharton’s Jelly (WJ-MSCs) condition temperature stress. METHODS AND RESULTS: On exposure 40°C, WJ-MSCs underwent cycle arrest with no significant change status, along an induction VTN expression both at mRNA protein levels. Interestingly, inhibition pro-survival signalling pathways, ERK or PI3K, 40°C led further upregulation without any impact on status. esiRNA mediated knockdown pathway inhibitors, resulted reduced cellular accompanied by reversal G0/G1 arrest. CONCLUSIONS: These results established as protective factor that maintained Finally, autophagy was indicated adopted executing its role.