Myocarditis is a common inflammatory cardiomyopathy, associated with cardiomyocyte apoptosis, which can lead to chronic left ventricular dysfunction. Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. Experimental and clinical studies consistently support the application of cellular transplantation as a strategy to improve myocardial function. Mesenchymal stromal cells (MSCs) mediate distinct paracrine effects supporting endogenous regeneration, but most important are their remarkable immunoregulatory properties. In this review, an overview of current knowledge on immunopathology in myocarditis will be given. Furthermore, current research regarding the immunomodulatory properties of MSCs in the context of myocarditis will be discussed. Finally, the impact of MSC priming by the environment on their functionality and the advantages of systemic administration of MSCs under myocarditis are outlined. 1. Introduction Inflammatory cardiomyopathy (myocarditis), present as an acute and/or a chronic inflammation of the heart, is associated with necrosis and degeneration of cardiomyocytes leading to subsequent cardiac dysfunction [1, 2]. Infections, systemic diseases, drugs, and toxins have been associated with the development of this disease. However, cardiotropic viruses such as Coxsackievirus 3 (CVB3) [3, 4], adenoviruses [5], and parvovirus B19 (B19) [6–8] are considered to be the main cause of inflammatory cardiomyopathy. The pathology of viral inflammatory cardiomyopathy results from the concomitant work between viral processes of propagation and the host immune responses in attempt to resist and fight against the virus. Both innate and adaptive immune responses are crucial determinants of the severity of myocardial damage, often associated with autoimmune responses against the heart tissue antigens. The overwhelming immune response contributes to the development of chronic myocarditis and dilated cardiomyopathy (DCM), a condition for which the only treatment option at end-stage is heart transplantation [9]. DCM is one of the most common causes of heart failure, contributing to the main mortality rate of cardiomyopathy [10]. Although the application of modern therapy options has led to improved mortality rate, only half of the patients survive for five years [11]. Immunosuppressive and immunomodulating therapy have shown a beneficial effect in chronic, virus-negative inflammatory cardiomyopathy [12, 13], while there
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