Immunomodulatory Effects of Mesenchymal Stromal Cells Revisited in the Context of Inflammatory Cardiomyopathy

Abstract

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.

Viral heart disease — treatment

“…Mesenchymal stem cells (MSC) are a heterogenous population of cells located mainly in the perivascular niches in almost all tissues [21]. MSC migrate to the site of inflammation, where the local micro-environment and cytokines (IFN-g, tumour necrosis factor a [TNF-a], IL-1a, or IL-1b) activate their immunomodulatory effects [21].…”

“…MSC migrate to the site of inflammation, where the local micro-environment and cytokines (IFN-g, tumour necrosis factor a [TNF-a], IL-1a, or IL-1b) activate their immunomodulatory effects [21]. MSC modulate the function of a great variety of immune cells [21].…”

“…MSC promote a Th2 phenotype, which is of great relevance for preventing the development of autoimmune heart disease. The formation of CD8+ T cells is inhibited, but activated CD8+ T cells are preserved with restricted killing of virally infected cells [21]. The generation of T regulatory cells is favoured, which ultimately leads to immune tolerance [21].…”

“…The formation of CD8+ T cells is inhibited, but activated CD8+ T cells are preserved with restricted killing of virally infected cells [21]. The generation of T regulatory cells is favoured, which ultimately leads to immune tolerance [21]. In the presence of MSC, plasmacytoid dendritic cells upregulate the release of the anti-inflammatory and cardioprotective cytokines IL-10 and IFN type I [21].…”

“…The generation of T regulatory cells is favoured, which ultimately leads to immune tolerance [21]. In the presence of MSC, plasmacytoid dendritic cells upregulate the release of the anti-inflammatory and cardioprotective cytokines IL-10 and IFN type I [21]. Generation of anti-inflammatory macrophages is encouraged, which is relevant for resolving the inflammation and for the prevention of the development of autoimmune MC [21].…”