Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Myocarditis

Myocarditis is an inflammatory disease of the heart. Immune cells of innate immunity (dendritic cells, macrophages, neutrophils, natural killer, and natural killer T cells) and acquired immunity (T and B lymphocytes) play a crucially important role in the development and progression of myocarditis. Mesenchymal stem cells (MSCs) are immunoregulatory cells that attenuate detrimental immune responses in inflamed hearts and alleviate ongoing inflammation due to their potent immunosuppressive properties. MSCs, in a paracrine manner, attenuate antigen-presenting properties of dendritic cells and macrophages, alleviate synthesis of reactive oxygen species and inflammatory cytokines in neutrophils and monocytes, prevent the generation of inflammatory CD4 + Th1 and Th17 cells, enhance the expansion of immunosuppressive T regulatory cells, and suppress the toxicity of CD8 + T lymphocytes, natural killer, and natural killer T cells. MSCs-based alteration of immune cells’ phenotype and function leads to the attenuation of myocarditis and the improvement of cardiac function. The beneficial effects of MSCs in alleviating myocarditis mainly rely on the biological effects of MSC-derived immunoregulatory proteins and growth factors. Most of them are contained within MSC-sourced exosomes, which easily bypass all biological barriers in the body due to their nano-sized dimension and a lipid envelope. Since many experimental and clinical studies demonstrated the therapeutic potential of MSCs and their exosomes in the treatment of myocarditis, in this chapter, we summarized current knowledge regarding molecular mechanisms responsible for the beneficial effects of MSCs and their exosomes in the treatment of the therapy of myocarditis.