High glucose microenvironment and human mesenchymal stem cell behavior

Core Tip

Core Tip: High glucose (HG) conditions, seen in vitro as well as in diabetic patients, adversely affect stem cells by disrupting mammalian target of rapamycin-phosphoinositide 3-kinase-Akt signaling, resulting in reduced cell survival and increased apoptosis. A recent study of adipose tissue-derived mesenchymal stem cells (MSCs) found dysregulation of this signaling pathway and defective mitochondrial membrane potential (MtMP) under HG conditions. This leads to decreased ATP production, heightened oxidative stress, and structural abnormalities, causing diminished cell survival. Altered mitochondrial NAD+/NADH redox state and disrupted mitochondrial homeostasis worsen the hostile microenvironment induced by HG exposure. These findings are a note of caution for using MSCs from hyperglycemic donors in cell-based therapy owing to their poor survival and proliferation rates. Future research targeting MtMP restoration may enhance the therapeutic efficacy of MSCs in hyperglycemic patients.