Human mesenchymal stem cells exhibit altered mitochondrial dynamics and poor survival in high glucose microenvironment

Abstract Background : Mesenchymal stem cells (MSCs) are reputable type of stem cells that has enchanted regenerative abilities and can be used to treat many chronic diseases. Diabetes mellitus (DM) is a frequently diagnosed chronic disease characterized by hyperglycemia which initiates many multisystem complications in the long-run. DM patients can benefit from MSCs transplantation to curb down the pathological consequences associated with hyperglycemia persistence and restore the function of damaged tissues. MSCs therapeutic outcomes are found to last for short period of time and ultimately these regenerative cells are eradicated and died in DM disease model. So it is necessary to investigate the impact of high glucose or hyperglycemia on the cellular and molecular characteristics of MSCs. Materials and Methods: Human adipose tissue –derived MSCs (hAD-MSCs) were seeded in low (5.6 mmol/L of glucose) and high glucose (25 mmol/l of glucose) for 7 days. Cytotoxicity, viability, mitochondrial dynamics, and apoptosis were deplored using specific kits. Western blotting was performed to measure the protein expression of PI3K, TSC1, and mTOR in these cells. Results : hAD-MSCs cultured in high glucose for 7 days demonstrated marked decrease in their viability. Mitcohondrial membrane potential and NAD+/NADH ratio were dropped in high glucose exposed hAD-MSCs indicating disturbed mitochondrial function. PI3K protein expression deceased in high glucose culture MSCs and it was coupled with upregulation in TSC 1 and downregulation in mTOR protein expression. Apoptosis was induced as a result of mitochondrial impairment and explained the poor survival of MSCs in high glucose. Conclusion: high glucose impaired the mitochondrial dynamics and regulatory proteins in hAD-MSCs ensuing their poor survival and high apoptosis rate in hyperglycemic microenvironment.