High glucose microenvironment and human mesenchymal stem cell behavior  

作　　者：Muhammad Abdul Mateen Nouralsalhin Alaagib Khawaja Husnain Haider 

机构地区：[1]Basic Sciences,Sulaiman AlRajhi University,AlQaseem 52736,Saudi Arabia [2]Cellular and Molecular Pharmacology,Sulaiman AlRajhi Medical School,Al Bukairiyah 51941,Saudi Arabia

出　　处：《World Journal of Stem Cells》2024年第3期237-244,共8页世界干细胞杂志（英文版）（电子版）

摘　　要：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 body.It interferes with diverse signaling pathways,i.e.mammalian target of rapamycin(mTOR)-phosphoinositide 3-kinase(PI3K)-Akt signaling,to impact physiological cellular functions,leading to low cell survival and higher cell apoptosis rates.While 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 production.This organelle-level dysfunction energy-starves the cells and increases oxidative stress and ultrastructural abnormalities.Disruption 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 HG.Some previous studies have also reported altered mitochondrial membrane polarity(causing hyperpolarization)and reduced mitochondrial cell mass,leading to perturbed mitochondrial homeostasis.The hostile microenvironment created by HG exposure creates structural and functional changes in the mitochondria,altering their bioenergetics and reducing their capacity to produce ATP.These are significant data,as MSCs are extensively studied for tissue regeneration and restoring their normal functioning in cell-based therapy.Therefore,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 proliferation.As 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 in hyperglycemic patients.

关 键 词：Adipose tissue APOPTOSIS BIOENERGETICS Cell survival Cell therapy HYPERGLYCEMIA MITOCHONDRIA Mesenchymal stem cells Stem cells 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]