Alpha-ketoglutarate enhances adipose-derived stem cells survival in wound healing by hypoxia-inducible factor 1-alpha-mediated redox homeostasis and glycogen-dependent bioenergetics

This study demonstrates that α-KG preconditioning significantly enhances ADSC survival and therapeutic efficacy in burn wound healing through HIF-1α-mediated metabolic reprogramming. HIF-1α activation coordinately upregulates glutamine-driven GSH synthesis for redox homeostasis and glycogen storage for bioenergetic resilience, providing a dual mechanism of cytoprotection. These findings establish metabolic preconditioning as a potent, translatable strategy to improve the efficacy of stem cell-based therapies not only in wound healing but potentially in other ischemic and inflammatory conditions characterized by poor cell survival.