Triple Hybrid Cellular Nanovesicles Promote Cardiac Repair after Ischemic Reperfusion.
Jialin LaiQi PanGuihao ChenYu LiuCheng ChenYuanwei PanLujie LiuBinglin ZengLing YuYunsheng XuJinyao TangYuejin YangLang RaoPublished in: ACS nano (2024)
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.
Keyphrases
- left ventricular
- mesenchymal stem cells
- acute myocardial infarction
- ejection fraction
- induced apoptosis
- aortic stenosis
- inflammatory response
- cell cycle arrest
- oxidative stress
- cerebral ischemia
- hypertrophic cardiomyopathy
- umbilical cord
- cardiac resynchronization therapy
- endothelial cells
- heart failure
- signaling pathway
- mouse model
- cell therapy
- left atrial
- public health
- mitral valve
- stem cells
- bone marrow
- gene expression
- copy number
- endoplasmic reticulum stress
- single cell
- acute ischemic stroke
- lipopolysaccharide induced
- transcatheter aortic valve replacement
- antiretroviral therapy
- cell proliferation
- aortic valve
- percutaneous coronary intervention
- pi k akt
- immune response