Butyrate-preconditioned human adipose-derived stem cell-conditioned medium enhances myocardial perfusion after infarction.

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)

Introduction Adipose-derived stem cell-conditioned medium (ASC-CM) is promising for cardiac repair via paracrine mechanisms. However, variability in efficacy limits its clinical translation. We investigated whether preconditioning human ASC with butyrate (ASC-BA-CM) enhanced its paracrine potency and improved in vitro and in vivo outcomes. Method RNA-sequencing of human ASCs treated with butyrate was performed to characterize transcriptomic changes. CM was collected and analyzed via cytokine/chemokine arrays. Wound healing assays using human umbilical vein endothelial cells (HUVECs), with and without THP-1 macrophage co-culture, were performed to evaluate endothelial repair and its correlations with secreted factors. In vivo angiogenesis was assessed using a sponge implantation model, and myocardial perfusion was measured in a rat myocardial infarction model using single-photon emission computed tomography/computed tomography (SPECT/CT) thallium-201 imaging. Results Butyrate preconditioning upregulated angiogenesis- and immune-related genes, including CXCL8 , SOD2 , and TGM2 . It increased IL-10, CXCL5, and MMP-1 secretion. In vitro , BA-preconditioned ASC-CM enhanced HUVEC wound closure, which was improved by co-culture with THP-1 macrophages and negatively correlated with TGFb3 and TIMP-2 levels. In vivo , ASC-BA-CM promoted vascularization and macrophage accumulation in spon

Evidence level

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

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