Reprogramming of Hypoxia‐Induced Metabolic Disorder in Mouse Kidneys by Mesenchymal Stem Cells Through Improving Mitochondrial Dynamics and Function

ABSTRACT Objective To assess the effects of human umbilical cord‐derived mesenchymal stem cells (hUC‐MSCs) on mitochondrial damage and metabolic disorders induced by acute and chronic hypoxia in mouse kidneys. Method Comprehensive analyses were conducted, including histopathology, mitochondrial morphology analysis, biochemical assessments, transcriptomics and metabolomics. Results The results revealed that hUC‐MSCs significantly improved renal mitochondrial integrity and maintained mitochondrial dynamic balance under both acute and chronic hypoxia. This improvement was achieved by upregulating the expression of peroxisome proliferator‐activated receptor gamma coactivator‐1 alpha, which ultimately enhanced mitochondrial function. Furthermore, hUC‐MSCs reprogrammed renal metabolic disorders, particularly improvements in urea and purine metabolic dysfunction, increased fatty acid oxidation and amelioration of lipid metabolic disorders. Conclusion These findings suggest that hUC‐MSCs could be part of a promising strategy for enhancing renal health and metabolic stability in individuals exposed to high altitudes or other hypoxic environments, highlighting their potential therapeutic value in addressing hypoxia‐induced mitochondrial damage and renal metabolic disorders.