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High glucose microenvironment and human mesenchymal stem cell behavior

World Journal of Stem Cells 2024年第3期16卷 237-244页

作者： Muhammad Abdul Mateen nouralsalhin alaagib Khawaja Husnain Haider Basic Sciences Sulaiman AlRajhi UniversityAlQaseem 52736Saudi Arabia Cellular and Molecular Pharmacology Sulaiman AlRajhi Medical SchoolAl Bukairiyah 51941Saudi Arabia

High glucose(HG)culture conditions in vitro and persistent exposure to hyperglycemia in diabetes patients are detrimental to stem cells,analogous to any other cell type in our *** interferes with diverse signaling pathways,*** target of rapamycin(mTOR)-phosphoinositide 3-kinase(PI3K)-Akt signaling,to impact physiological cellular functions,leading to low cell survival and higher cell apoptosis *** elucidating the underlying mechanism responsible for the apoptosis of adipose tissue-derived mesenchymal stem cells(MSCs),a recent study has shown that HG culture conditions dysregulate mTORPI3K-Akt signaling in addition to mitochondrial malfunctioning due to defective mitochondrial membrane potential(MtMP)that lowers ATP *** organelle-level dysfunction energy-starves the cells and increases oxidative stress and ultrastructural *** of the mitochondrial electron transport chain produces an altered mitochondrial NAD+/NADH redox state as evidenced by a low NAD+/NADH ratio that primarily contributes to the reduced cell survival in *** previous studies have also reported altered mitochondrial membrane polarity(causing hyperpolarization)and reduced mitochondrial cell mass,leading to perturbed mitochondrial *** hostile microenvironment created by HG exposure creates structural and functional changes in the mitochondria,altering their bioenergetics and reducing their capacity to produce *** are significant data,as MSCs are extensively studied for tissue regeneration and restoring their normal functioning in cell-based ***,MSCs from hyperglycemic donors should be cautiously used in clinical settings for cell-based therapy due to concerns of their poor sur-vival rates and increased rates of post engraftment *** hypergly-cemia alters the bioenergetics of donor MSCs,rectifying the loss of MtMP may be an excellent target for future research to restore the normal functioning of MSCs i

关键词： Adipose tissue Apoptosis Bioenergetics Cell survival Cell therapy Hyperglycemia Mitochondria Mesenchymal stem cells Stem cells

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