High glucose microenvironment and human mesenchymal stem cell behavior

被引:4
作者
Mateen, Muhammad Abdul [1 ]
Alaagib, Nouralsalhin
Haider, Khawaja Husnain [2 ,3 ]
机构
[1] Sulaiman Al Rajhi Univ, Basic Sci, Al Qaseem 52736, Saudi Arabia
[2] Sulaiman Al Rajhi Med Sch, Cellular & Mol Pharmacol, Al Bukairiyah 51941, Saudi Arabia
[3] Sulaiman Al Rajhi Med Sch, Cellular & Mol Pharmacol, POB 777, Al Bukairiyah 51941, Saudi Arabia
来源
WORLD JOURNAL OF STEM CELLS | 2024年 / 16卷 / 03期
关键词
Adipose tissue; Apoptosis; Bioenergetics; Cell survival; Cell therapy; Hyperglycemia; Mitochondria; Mesenchymal stem cells; Stem cells; MITOCHONDRIAL DYNAMICS; PROLIFERATION; APOPTOSIS; DIFFERENTIATION; HYPERGLYCEMIA; CONNEXIN-43; SURVIVAL; IMPAIRS; STRESS; MTOR;
D O I
10.4252/wjsc.v16.i3.237
中图分类号
Q813 [细胞工程];
学科分类号
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 mTOR-PI3K-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 survival rates and increased rates of post engraftment proliferation. As hyperglycemia 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.
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页数:9
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