New study focuses on creating thymosin β4 loaded monocyte membrane-modified extracellular vesicles (Tβ4-MmEVs) for heart repair post-myocardial infarction (MI), exhibiting targeted delivery to damaged regions, resulting in enhanced cardiomyocyte and endothelial cell proliferation both in vitro and in vivo. Treatment with Tβ4-MmEVs in mice showed significant improvement in cardiac function post-MI, with reduced myocardial fibrosis and increased vascular density observed.

In this study, cell membrane-modified extracellular vesicles (MmEVs) were developed for heart repair by modifying cardiac-resident macrophage-derived extracellular vesicles (mEVs) with monocyte membranes. This modification allowed for immune evasion and targeted localization to damaged regions by expressing CD47 on MmEVs and leveraging the affinity between monocyte membrane proteins and damaged cardiomyocytes and endothelial cells. The MmEVs were designed to evade phagocytosis by the mononuclear phagocytic system (MPS) and effectively target the damaged heart, hence enhancing cardiomyocyte proliferation and endothelial cell migration. These targeted nanoparticles have shown significant potential for myocardial infarction (MI) adjuvant therapy, offering new possibilities for cardiac repair and regeneration.

To further improve cardiac function post MI, researchers developed modified extracellular vesicles loaded with thymosin β4 (Tβ4-MmEV) for heart repair. These EVs were engineered with monocyte membranes to target damaged areas and evade the immune system, resulting in reduced scar tissue and increased blood vessel density in MI mice. 

Tβ4-MmEVs improved the viability of hypoxic cardiomyocytes compared to other interventions by presenting a higher survival rate in oxygen-glucose deprivation (OGD) conditions. When cardiomyocytes were treated with Tβ4-MmEVs for 8 hours, they showed a higher survival rate in OGD conditions than the groups treated with phosphate-buffered saline (PBS) and MmEVs. Additionally, the TUNEL assay results demonstrated that Tβ4-MmEVs significantly inhibited cardiomyocyte apoptosis compared to the PBS and MmEVs groups, with the latter showing more pronounced apoptotic effects. Furthermore, immunofluorescence staining showed that cardiomyocytes co-cultured with Tβ4-MmEVs significantly increased the expression of proliferation markers PH3 and Ki67 compared to other interventions, indicating that Tβ4-MmEVs greatly increased cardiomyocyte proliferative capacity.

Tβ4 and MmEVs improved endothelial cell migration and proliferation in vitro by significantly enhancing endothelial cell viability, proliferation, and migration under hypoxic conditions. Through CCK8 assays and immunofluorescence staining, it was observed that Tβ4-MmEVs increased the survival rate of endothelial cells in hypoxic conditions compared to PBS and MmEVs groups.

The results of animal experiments involving MI mice treated with MmEVs and Tβ4-MmEVs showed promising outcomes. Specifically, the study revealed that mice treated with Tβ4-MmEVs displayed a notable increase in the contraction index compared to other groups, as observed through improved myocardial contractions on ultrasound imaging.

These findings collectively suggest that the targeted nanoparticles, Tβ4-MmEVs, have significant potential for MI adjuvant therapy. By enhancing cardiomyocyte proliferation, promoting endothelial cell migration, and reducing myocardial fibrosis, these modified EVs hold promise for improving cardiac repair and regeneration post-myocardial infarction.

Whole article can be found here: https://doi.org/10.1016/j.actbio.2023.08.022