Cardioprotective effects of rat adipose‑derived stem cells differ under normoxic/physioxic conditions and are�associated with paracrine factor secretion

Abstract

Adipose tissue-derived stem cells (AScs) are beneficial for myocardial regeneration. The physiological oxygen content of human organs is estimated to range between 1 and 11%. However, in the majority of previous in vitro studies with cultured ASCs, the O 2 concentration was artificially set to 21%. The present study aimed to compare the protective effects of rat ASCs on neonatal rat ventricular myocytes (NRVMs) under normoxic (21% O 2 ) and physioxic (5% O 2 ) conditions. Rat NRVMs cultured under normoxia or physioxia were treated with H 2 O 2 or left untreated, and further co-cultured with ASCs in 21% or 5% O 2 . The apoptosis of NRVMs was evaluated by Annexin V staining and quantitating the protein levels of Bcl-2 and Bax by western blotting. The oxidative stress of NRVMs was determined by a glutathione/oxidized glutathione assay kit. The concentrations of secreted vascular endothelium growth factor (VEGF), insulin like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) in the culture medium were quantified by enzyme-linked immunosorbent assay. Under both normoxia and physioxia, co-culture with ASCs protected H 2 O 2 -exposed NRVMs from apoptosis and significantly alleviated the oxidative stress in NRVMs. The protective effects of ASCs were associated with increased secretion of VEGF, IGF-1 and bFGF. ASCs cultured in 5% O 2 exhibited certain cardioprotective effects against H 2 O 2 stress. The results of the present study suggested that O 2 concentrations influenced the cardioprotective effects of ASCs. VEGF, IGF-1 and bFGF may serve a role in the myocardial regeneration mediated by transplanted ASCs.

Hypoxia and metabolic inhibitors alter the intracellular ATP:ADP ratio and membrane potential in human coronary artery smooth muscle cells

“…Therefore, most of the contemporary experiments using in vitro cell culture are conducted with oxidatively stressed cells. Culture in hyperoxic conditions has conferred a protective resilience to many kinds of oxidative stressors, which is thought to be an artefact arising from the current culture leading to poor translation of investigations from in vitro to in vivo (Ferguson et al, 2018;Lin et al, 2020). On the contrary, the extent of antioxidant enzyme activities and redox homeostasis are examined to be closer to in vivo conditions if the cells are pre-conditioned under physioxia (Pastore et al, 2001;Shindo et al, 1994).…”

Adipose-derived stem cells ameliorate radiation-induced lung injury by activating the DDAH1/ADMA/eNOS signaling pathway

“…showed that coculture with ASCs protects neonatal rat ventricular myocytes from apoptosis caused by H 2 O 2 treatment and significantly reduces oxidative stress under normoxic and hyperoxic conditions [ 29 ]. The protective effect of ASCs is related to increasing secretion of VEGF, IGF-1, and bFGF [ 30 ]. Additionally, extracellular vesicles secreted by ASCs attenuate PM2.5-induced apoptosis and necrosis of alveolar type II epithelial cells and improve lung injury and pulmonary fibrosis.…”