MSC-exosomes pretreated by Danshensu extracts pretreating to target the hsa-miR-27a-5p and STAT3-SHANK2 to enhanced antifibrotic therapy

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 Peritoneal fibrosis (PF) is a serious complication commonly associated with prolonged peritoneal dialysis. Mesenchymal stem cells (MSCs) and their exosomes (Exo) have shown significant therapeutic promise in treating fibrotic conditions. Danshensu (DSS), a bioactive compound from the traditional Chinese herb Danshen reverses fibrosis. This study aims to investigate a novel strategy to enhance the therapeutic efficacy against PF by DSS preconditioning MSCs-derived exosomes (DSS-Exo). Methods The in vitro studies included the effects of DSS duration on MSCs, and the characterization of DSS-Exo and Exo, followed by the assessment of RNA and protein expression levels of peritoneal fibrosis markers and inflammatory cytokines levels after treating human peritoneal mesothelial (HMrSV5) cells. In vivo experiments were conducted on a PF mouse model to observe cell morphology, collagen deposition, fibrosis localization, and to evaluate peritoneal functions such as filtration rate, urea nitrogen clearance, peritoneal thickness, and protein leakage. Mechanistic insights were gained through the analysis of the STAT3/HIF-1α/VEGF signaling pathway, tissue dual-fluorescence localization,chromatin immunoprecipitation sequencing (ChIP-seq), and dual-luciferase reporter (DLR) assays. Additionally, the differential expression of miRNAs between DSS-Exo and Exo was explored and validation

Evidence level

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

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