Therapeutic Influence of Exosomes Derived from Non-heat versus Heat Shocked Stem Cells on Experimentally Induced Myocardial Infarction in Adult Male Albino Rats

Abstract

Background: Worldwide, myocardial infarction (MI) is considered as a principal cause of mortality. It results in death of the cardiac myocytes and declining of the cardiac functions. Exosomes of the bone marrow mesenchymal stem cells (BMMSCs) are cell-free, nano-sized extracellular vesicles that have the same reparative potentiality of the stem cells. Heat shock is one of the stresses that increase the production of heat shock proteins in the stem cells augmenting their survival capabilities. Aim of the Work: The current study aimed at assessing and comparing the therapeutic potentiality of exosomes derived from the non-heat and the heat shocked BMMSCs (non-HSBMMSCs-EXOs and HSBMMSCs-EXOs) on experimentally induced MI (acute & chronic stages) with underlining the probable explanation for that difference.Materials and Methods: 56 adult male albino rats were divided into the donor group (for non-HSBMMSCs-EXOs & HSBMMSCs-EXOs preparation) and the experimental groups (control, MI, MI-non-HSBMMSCs-EXOs & MI-HSBMMSCs-EXOs). Four control rats with two rats from each MI-non-HSBMMSCs-EXOs & MI-HSBMMSCs-EXOs groups were sacrificed 1 day following MI to confirm BMMSCs homing while other rats were sacrificed after 3 &28 days. Serological, biochemical, histological and morphometric studies were done.Results: The acute stage of MI revealed degenerative and inflammatory features whereas the chronic stage demonstrated marked fibrotic changes. Such changes were regressed in MI-non-HSBMMSCs-EXOs & MI-HSBMMSCs-EXOs groups except that of MI-non-HSBMMSCs-EXOs sacrificed after 28 days.Conclusion: Both non-HSBMMSCs-EXOs and HSBMMSCs-EXOs had therapeutic capabilities in the acute stage of MI which was more evident with HSBMMSCs-EXOs. In the chronic stage, non-HSBMMSCs-EXOs exhibited non-curative effect despite the perfect effect of HSBMMSCs-EXOs.