Cardiac tissue regeneration by modulation of mitochondrial bioactivity in the Rat model of infarction

Abstract

Today, ischemic heart diseases are considered one of the main problems in the field of human health. Developing new cellular product methods has brought new hopes to treating patients with cardiac ischemia. This study aims to investigate the effect of mitochondria activated with dichloroacetate and metformin drugs extracted from mesenchymal stem cells (MSCs) on the infarcted rat model. With the hypothesis that the transplantation of activated mitochondria improves the potential of angiogenesis and regeneration in the repair and function of the infarcted heart. Methods: For this purpose, male Wistar rats were divided into five groups (control and treatment) and examined at 14 days. After induction of acute infarct, mitochondria activated by metformin and dichloroacetate drugs were extracted from MSCs and injected into groups with or without hydrogel in 3 areas (around the infarct or border). After 14 days, the heart was removed. To investigate angiogenesis by immunohistochemical technique, the amount of vWF and α-SMA factors and the extent of the fibrosis area were checked using Mason trichrome staining and H&E staining. The amount of blood enzymes was also measured in the blood of rats of different groups after 14 days. Result: In this study, the findings indicate that injecting active mitochondria extracted from mesenchymal stem cells can restore and improve heart function in the infarcted area. According to Masson's trichrome staining, the thickness of the anterior wall of the left ventricle was significantly increased in groups with mitochondrial injection (Mito), hydrogel (Alg/Gel), and Mito + Alg/Gel compared to the stroke group (MI) (p < 0.0001). The increase of angiogenic factor (vWF) and the density of capillaries (α-SMA) showed a similar trend, in which the number and density of capillaries in the Mito + Alg/Gel group was the highest compared to the other groups, especially the MI group (p < 0.0001). AST, ALT, and LDH enzymes were examined in different groups, 14 days after MI, no significant difference was observed between the groups that received Mito + Alg/Gel and the other groups (P>0.05).