Clinical significance of increased levels of endogenous Muse cells in the myocardium of patients with fulminant myocarditis

Abstract Background: The significance of Muse cells, stress-tolerant endogenous pluripotent-like reparative stem cells involved in tissue repair, in acute myocarditis has not been evaluated. Methods: Muse (SSEA-3+) cells/area were counted in biopsied myocardial tissue samples from 17 patients with fulminant myocarditis (51±19 years) and 6 with non-inflammatory myocardial disease (69±5 years, control). Patients were segregated according to clinically and histopathologically relevant items, and further segregated by median values of echocardiographic parameters and biomarkers in acute and recovery phases for stratification into Yes/No groups. Categorical variables with binary values were assigned Yes or No and continuous variables were stratified based on the median value (values indicating more critical status or poorer recovery assigned to the Yes group). Results: Compared with controls, patients with fulminant myocarditis had significantly more Muse cells (P=0.00042). Patients with mechanical circulatory support (P=0.006), myocardial degeneration (P=0.023), and an acute-phase creatine kinase-myocardial band (CK-MB) level >71 U/L, indicating more critical status, had significantly more Muse cells (P=0.008). Patients with a higher acute/recovery phase ratio (indicator of recovery) of CK-MB <15.2 and cardiac troponin I 0.10 mg/dL during recovery had a lower Muse cell number than patients with CRP <0.10 (P=0.046). Conclusions: Muse cell number in acute phase myocardium biopsy specimens correlated with the severity of clinical features in the acute phase and the recovery from myocardial damage in the chronic phase. Myocardial biopsy combined with Muse cell detection by anti-SSEA-3 staining might be useful for evaluating disease severity and predicting treatment responsiveness in fulminant myocarditis.