Allogeneic Transplantation of Fetal Membrane-Derived Mesenchymal Stem Cells: Therapy for Acute Myocarditis

Abstract

Acute myocarditis is an acute inflammatory disease of the myocardium for which there is currently no specific treatment. Inflammatory cells also play a role in the onset of myocarditis. Mesenchymal stem cells (MSC) have immunomodulatory properties, which make them an attractive cell source for treatment of myocarditis, given the importance of the inflammatory component in this disorder. Autologous transplantation of bone marrow-derived MSC (BM-MSC) significantly reduced myocardial inflammation and cardiac dysfunction in a rat model of acute autoimmune myocarditis by reducing inflammation and stimulating angiogenesis. However, BM aspiration procedures are invasive and can yield low numbers of MSC after processing. Recently, the focus has been on allogeneic MSC transplantation, and fetal membranes (FMs) as an alternative source of MSC are expected to provide a large number of cells. We demonstrated that allogeneic FM-derived MSC (FM-MSC) transplantation also reduced myocardial inflammatory cell infiltration and cardiac dysfunction in a rat model of acute autoimmune myocarditis and that myosin-responsive T cell proliferation and activation were suppressed by FM-MSC. The transplantation of allogeneic FM-MSC did not elicit any lymphocyte proliferative response despite their allogeneic origin. Although further experiments are needed to apply the current results to human cell therapy, allogeneic FM-MSC transplantation may provide a new therapeutic strategy for the treatment of acute myocarditis. This review focuses on the immunomodulatory effects of MSC and discusses the potential of allogeneic FM-MSC transplantation therapy in acute myocarditis.