Background: The treatment method based on the use of stem cells to improve the symptoms of patients with heart attack was first reported in 2001. Since then, the use of stem cells from different sources in patients with cardiovascular diseases has been considered. In addition to their ability to differentiate, MSCs also have the capacity to modulate the function of the immune system, which has made them an attractive therapeutic tool. In recent decades, the importance of innate and acquired immune responses in the control of myocardial function has been seriously discussed during health and diseases. It has been shown that dysregulation of the immune system can lead to the induction of local devastating immune responses and trigger inflammatory events causing serious side effects associated with acute MI. IDO1 is a key enzyme in the tryptophan catabolism pathway. The immunomodulatory role of this enzyme has been reported in several studies and conditions, including pregnancy, chronic infection, autoimmune diseases, organ transplantation, and drug resistance in a variety of cancers. Methods: A rat model of heart attack was created based on the cryo method and injection of hTRET-IDO1 cells and their Exosomes in the desired heart area, then histological examinations and immune cells examination were performed by CBC test and differential white blood cell count. Repair of heart damage was also evaluated by echocardiography on day before surgery and days 1, 28, 55.and TTC test.was done. Results: In this study, it was shown that by modulating the immune system and reducing inflammation by cells and Exosomes with the IDO1 gene, the repair of heart damage in the heart attack model is significantly increased. Conclusion: For a long time, inflammation has been considered as a main factor in the development of atherosclerosis. Inflammatory cells and soluble mediators play an important role in creating arterial platelets. Based on this, targeting inflammatory pathways effectively reduces atherosclerosis in animal models of cardiovascular diseases. In the conditions of inflammation, the presence of pro-inflammatory cytokines are essential for the activation and calling of functional cells of the immune system and the regeneration of damaged tissue. The problem appears when the level of pro-inflammatory cytokines continuously increases and rises above the appropriate level. In this case, instead of calling progenitor cells to the damaged tissues, autoimmune responses are created and inflammatory mechanisms destroy the tissue structure. So by modulating the immune system, it is possible to increase cardiac function.

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