1 research outputs found
Triple Hybrid Cellular Nanovesicles Promote Cardiac Repair after Ischemic Reperfusion
The
management of myocardial ischemia/reperfusion (I/R) damage
in the context of reperfusion treatment remains a significant hurdle
in the field of cardiovascular disorders. The injured lesions exhibit
distinctive features, including abnormal accumulation of necrotic
cells and subsequent inflammatory response, which further exacerbates
the impairment of cardiac function. Here, we report genetically engineered
hybrid nanovesicles (hNVs), which contain cell-derived nanovesicles
overexpressing high-affinity SIRPα variants (SαV-NVs),
exosomes (EXOs) derived from human mesenchymal stem cells (MSCs),
and platelet-derived nanovesicles (PLT-NVs), to facilitate the necrotic
cell clearance and inhibit the inflammatory responses. Mechanistically,
the presence of SαV-NVs suppresses the CD47-SIRPα interaction,
leading to the promotion of the macrophage phagocytosis of dead cells,
while the component of EXOs aids in alleviating inflammatory responses.
Moreover, the PLT-NVs endow hNVs with the capacity to evade immune
surveillance and selectively target the infarcted area. In I/R mouse
models, coadministration of SαV-NVs and EXOs showed a notable
synergistic effect, leading to a significant enhancement in the left
ventricular ejection fraction (LVEF) on day 21. These findings highlight
that the hNVs possess the ability to alleviate myocardial inflammation,
minimize infarct size, and improve cardiac function in I/R models,
offering a simple, safe, and robust strategy in boosting cardiac repair
after I/R