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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Adipose-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. Aim To 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 h

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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