摘要
The administration of extracellular vesicles(EV)from mesenchymal stromal cells(MSC)is a promising cell-free nanotherapy for tissue repair after myocardial infarction(MI).However,the optimal EV delivery strategy remains undetermined.Here,we designed a novel MSC-EV delivery,using 3D scaffolds engineered from decellularised cardiac tissue as a cell-free product for cardiac repair.EV from porcine cardiac adipose tissue-derived MSC(cATMSC)were purified by size exclusion chromatography(SEC),functionally analysed and loaded to scaffolds.cATMSC-EV markedly reduced polyclonal proliferation and pro-inflammatory cytokines production(IFNγ,TNFα,IL12p40)of allogeneic PBMC.Moreover,cATMSC-EV recruited outgrowth endothelial cells(OEC)and allogeneic MSC,and promoted angiogenesis.Fluorescently labelled cATMSC-EV were mixed with peptide hydrogel,and were successfully retained in decellularised scaffolds.Then,cATMSC-EV-embedded pericardial scaffolds were administered in vivo over the ischemic myocardium in a pig model of MI.Six days from implantation,the engineered scaffold efficiently integrated into the post-infarcted myocardium.cATMSC-EV were detected within the construct and MI core,and promoted an increase in vascular density and reduction in macrophage and T cell infiltration within the damaged myocardium.The confined administration of multifunctional MSC-EV within an engineered pericardial scaffold ensures local EV dosage and release,and generates a vascularised bioactive niche for cell recruitment,engraftment and modulation of short-term post-ischemic inflammation.
