Comparison of the anti-inflammatory effects of mesenchymal stem cells and their exosomes on interleukin 1 induced inflammation of cardiac tissue in rats

Abstract

Nowadays, inflammatory and autoimmune diseases are notably prevalent, and inflammation also affects cardiac patients. Mesenchymal stem cells (MSCs), with their immunemodulating properties, have various applications in regenerative medicine. Recently, therapeutic effects of MSCs in exosomes derived from these cells have also been observed. The tumorigenic properties, lower immune stimulation, reduced dosage response, and easier control have increased the popularity of exosomes. Materials and methods: Inflammation in cardiac tissue was induced in rats using interleukin 1 beta (IL-1β) through intraperitoneal injection at a dose of 10 μg/kg for six consecutive days. The animals were divided into three groups: IL-1β, cells, and exosomes. Adipose-derived stem cells (ASCs) and exosomes obtained from these cells were injected into the rats’ venous circulation after isolation and identification via flow cytometry. Seven days post-treatment, cardiac samples from these animals, along with the control group, were collected. Tissue preparation was conducted using H&E staining, Trichrome Mason and immunohistochemistry with antibodies (Bax, Bcl2, CD68, and αSMA), and examined under a light microscope. Results: H&E staining results indicated that IL-1β caused moderate acute inflammation in cardiac tissue. Additionally, a decrease in the striation of cardiomyocytes, displacement of their nuclei from the center to the periphery, and sometimes necrosis and nuclear deformation were observed. Edema in the extracellular matrix, leukocyte infiltration, RBCs exiting capillaries due to endothelial damage, and loss of capillary wall integrity were noted. Immunohistochemical analysis with BCL2 and BAX markers confirmed the occurrence of apoptosis in myocytes with peripheral and dense nuclei. Endothelial disruption was also observed with positive BAX cells. CD68-positive macrophages in cardiac tissue exposed to IL-1β were increased compared to controls. Interleukin-1 caused an increase in tissue fibroblasts, and the expression of αSMA indicated increased actin in these cells and their differentiation into myofibroblasts, which increase under tissue injury conditions. Masson’s trichrome staining did not show any fibrosis resulting from IL-1β injection, indicating that there was insufficient time for collagen production within the one-week study period during which acute cardiac inflammation was established. Microscopic observations from routine staining and BCL2, BAX, CD68, and αSMA showed that intravenous injection of ASCs and exosomes derived from these cells partially improved tissue repair with adipose-derived stem cells; however, exosomes exhibited better improvement results.