Mononuclear cell secretome protects from experimental autoimmune myocarditis

Abstract

AimsSupernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model.Methods and resultsBALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells.ConclusionMNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases.

Autoimmune myocarditis is not associated with left ventricular systolic dysfunction

“…4 In order to investigate the pathophysiologic mechanisms behind this devastating disease, various animal models have been developed and are now frequently used in the scientific field. 7,8 In addition to the histopathological examination, the effect of applied therapeutic remedies is then frequently assessed by transthoracic echocardiography (TTE), which depicts the macroscopic and functional sequelae of underlying pathophysiologic processes. 5,6 The majority of the immunized animals then develop a CD4+ cell-mediated experimental autoimmune myocarditis (EAM) peaking 21 days after the first immunization, despite no apparent clinical symptoms of heart failure.…”

Peripheral Blood Mononuclear Cell Secretome for Tissue Repair

“…This second undesirable phase of spinal cord injury consists of a multilayered and complex combination of inflammatory pathways that are thought to drive ongoing tissue damage via enzymatic degradation, oxidative stress, and blood-brain infiltrate, offering a novel treatment option in an experimental myocarditis model. The authors showed that PBMC-S induced caspse-8-dependent apoptosis of autoreactive CD-4-positive T-cells, leading to remission of the decorative autoimmune processes [100] in a well-defined myocarditis model. The immunomodulatory effects of PBMC-S were further evaluated by Kasiri et al [107].…”

Peripheral blood mononuclear cell secretome for tissue repair

“…Mice receiving apoptotic PBMC–S at the clinical onset of disease had reduced lymphocytic infiltrate, offering a novel treatment option in an experimental myocarditis model. The authors showed that PBMC-S induced caspse-8-dependent apoptosis of autoreactive CD-4-positive T-cells, leading to remission of the decorative autoimmune processes [100] in a well-defined myocarditis model.…”