ArticleWorld journal of stem cells2026
Alpha-ketoglutarate enhances adipose-derived stem cells survival in wound healing by hypoxia-inducible factor 1-alpha-mediated redox homeostasis and glycogen-dependent bioenergetics.
Article in World journal of stem cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAdipose-derived stem cells (ADSCs) hold significant therapeutic potential for regenerative medicine, particularly in wound healing, owing to their multipotency, paracrine activity, and relative abundance. However, the clinical application of ADSC-based therapies is substantially limited by the harsh microenvironment of acute wounds, characterized by hypoxia, nutrient deprivation, and oxidative stress, which leads to massive apoptotic cell death post-transplantation. Preconditioning strategies to enhance cellular resilience have thus gained considerable interest. Recent insights from cancer biology highlight the crucial role of metabolic reprogramming, orchestrated by hypoxia-inducible factor-1α (HIF-1α), in promoting survival under stress. Our previous work demonstrated that preconditioning with α-ketoglutarate (α-KG) enhances ADSC survival and accelerates wound healing, purportedly through HIF-1α upregulation. Nevertheless, the precise metabolic mechanisms by which α-KG preconditioning confers cytoprotection remain incompletely elucidated.
aimTo investigate the mechanistic role of HIF-1α in mediating the enhanced survival and regenerative capacity of α-KG-preconditioned ADSCs in an acid burn wound model. Specifically, we sought to determine whether HIF-1α activation drives complementary adaptations in glutamine and glycogen metabolism to maintain redox and energy homeostasis, respectively, under the multifactorial stress conditions of a wound.
methodsHuman ADSCs were isolated from lipoaspirates and preconditioned with dimethyl-α-KG.
resultsα-KG preconditioning significantly enhanced the survival of ADSCs both
conclusionThis 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.
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