Extracellular vesicle-enriched secretome of adipose-derived stem cells upregulates clusterin to alleviate doxorubicin-induced apoptosis in cardiomyocytes.

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)

Doxorubicin (DOX) is a potent chemotherapeutic widely used against various cancers, but its clinical application is limited by DOX-induced cardiotoxicity (DIC). This study explored the cardioprotective potential of extracellular vesicle-enriched secretome derived from adipose stem cells (EVS ASC ) in mitigating DOX-induced apoptosis in cardiomyocytes. Adipose-derived stem cells were cultured, and their conditioned medium and extraceullular vesicles were isolated and characterized according to the Minimal Information for Studies of Extracellular Vesicles 2023 guidelines. HL-1 cardiomyocytes were pretreated with EVS ASC before exposure to 1 µM DOX. Cell viability was assessed via the cell counting kit-8 assay, while apoptosis markers and survival mediators were evaluated through Western blotting. RNA sequencing identified differentially expressed genes, including clusterin (Clu), which was further quantified using an enzyme-linked immunosorbent assay. The functional role of clusterin was validated through siRNA-mediated knockdown. EVS ASC significantly improved cell viability in DOX-exposed cardiomyocytes and reduced the cleaved caspase-3 to procaspase-3 ratio. Clusterin expression was highest in EVS ASC -treated cells, and its knockdown markedly increased caspase-3 cleavage, confirming its pivotal role in cardioprotection. Moreover, EVS ASC enhanced the phosphorylation of AKT, B

Evidence level

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

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