Mesenchymal Stem Cell-Derived Extracellular Vesicles Alone or in Conjunction With a Sdkp-Conjugated Self-Assembling Peptide Improve a Rat Model of Myocardial Infarction Publisher Pubmed



Firoozi S^{1, 2} ; Pahlavan S³ ; Ghanian MH² ; Rabbani S⁴ ; Barekat M⁵ ; Nazari A³ ; Pakzad M³ ; Shekari F^{3, 7} ; Hassani SN³ ; Moslem F³ ; Lahrood FN³ ; Soleimani M⁶ ; Baharvand H^{3, 7}
Source: Biochemical and Biophysical Research Communications Published:2020

Abstract

Purpose: The aim of this study was to investigate the cardiac repair effect of human bone marrow mesenchymal stromal cells-derived extracellular vesicles (MSC-EVs) after intramyocardial injection in free form or encapsulated within a self-assembling peptide hydrogel modified with SDKP motif, in a rat model of myocardial infarction (MI). Methods: MSC-EVs were isolated by ultracentrifuge and characterized for physical parameters and surface proteins. Furthermore, cellular uptake and cardioprotective effects of MSC-EVs were evaluated in vitro using neonatal mouse cardiomyocytes (NMCMs). In vivo effects of MSC-EVs on cardiac repair were studied in rat MI model by comparing the vehicle group (injected with PBS), EV group (injected with MSC-EVs) and Gel + EV group (injected with MSC-EVs encapsulated in (RADA)4-SDKP hydrogel) with respect to cardiac function and fibrotic area using echocardiography and Masson's trichrome staining, respectively. Histological sections were assessed by α-SMA and CD68 immunostaining to investigate the angiogenic and anti-inflammatory effects of the MSC-EVs. Results: We observed the uptake of MSC-EVs into NMCMs which led to NMCMs protection against H2O2-induced oxidative stress by substantial reduction of apoptosis. In myocardial infarcted rats, cardiac function was improved after myocardial injection of MSC-EVs alone or in conjunction with (RADA)4-SDKP hydrogel. This functional restoration coincided with promotion of angiogenesis and decrement of fibrosis and inflammation. Conclusion: These data demonstrated that MSC-EVs can be used alone as a potent therapeutic agent for improvement of myocardial infarction. © 2020 Elsevier Inc.