Exosomal-ribosomal proteins-driven heterogeneity of epicardial adipose tissue derived stem cells under ischemia for cardiac regeneration.

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)

Extracellular ribosomal proteins secreted in exosomes elicit biological/regenerative responses; however, ribosomal proteins contained in the exosomes of ischemia-challenged epicardial adipose tissue-derived stem cells (EATDS) remain unexplored. This study focuses on the identification of ribosomal proteins in the exosomes of ischemia-challenged EATDS and their sub-populations based on the key ribosomal proteins using single-cell genomics. Exosomes were isolated from control, ischemic (ISC), and reperfused (ISC/R) EATDS harvested from hyperlipidemic microswine, and the proteins were detected using Liquid chromatography with tandem mass spectrometry (LC-MS/MS). One hundred ninety-nine proteins and 177 proteins were detected in ISC and ISC/R groups, respectively with significant fold-change compared to controls. Five ribosomal proteins, RPL10A, 40SRPS18, 40SRPS30, 60SRPL14, and 40SRPSA, were significant owing to their abundance based on LC-MS/MS data. Expression of these proteins, except RPL10A, at transcript and protein levels were lower in ISC group compared to the control. scRNAseq analysis revealed EATDS heterogeneity based on the upregulation of 40SRPSA, 40SRPL18, and 40SRPS18. Pro-inflammatory sub-populations upregulated CCL5, anti-inflammatory sub-population upregulated IL-11, proliferative sub-population upregulated cell cycle and DNA replication mediators, and non-prolife

Evidence level

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

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