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Platelet membrane-fusing MSC-derived apoptotic extracellular vesicles enhanced cardiac repair after ischemia/reperfusion injury
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DOI：10.1007/s13346-026-02178-7.png)
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Abstract
En 中文
Myocardial ischemia/reperfusion injury (I/RI) is a common complication following percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Mesenchymal stem cell-derived apoptotic vesicles (MSC-apoVs) seem to be a promising cell-free therapy for alleviating cardiac I/RI, but their therapeutic efficiency is hindered by insufficient targeting capability in vivo. The present study aims to explore the platelet membrane-modified apoVs (P-apoVs), utilizing the nature affinity of platelets for apoV delivery to the injured vascular and myocardial sites. P-apoVs exhibited excellent physicochemical properties, and microRNA (miRNA)-sequencing showed that the extrusion process had no detrimental effects on the content and distribution of miRNAs. Compared to non-modified apoVs, the cellular uptake of P-apoVs was greatly enhanced in bone marrow-derived macrophages (BMDMs), human umbilical vein endothelial cells (HUVECs) stressed by oxygen glucose deprivation/reperfusion (OGD/R) and neonatal rat cardiomyocytes (NRCMs) stressed by OGD/R. Functionally, P-apoVs inhibited the apoptosis of OGD/R NRCMs, promoted BMDM polarization toward M2 phenotype, as well as enhanced HUVEC migration and tube formation in vitro. In the myocardial I/RI model, P-apoVs preferentially accumulated in the injured myocardial sites and attenuate cardiac modeling after I/RI without systemic toxicity. In conclusion, this engineering platelet-modified apoVs shows potential as a therapeutic strategy for myocardial I/RI.
Keywords:
Myocardial ischemia/reperfusion injury
Apoptotic vesicles
Platelet-mimetic
Targeted delivery
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