Accumulation of endogenous Muse cells in the myocardium and its pathophysiological role in patients with fulminant myocarditis

Multi-lineage differentiating stress-enduring (Muse) cells, identified as pluripotent surface marker SSEA-3(+) cells, are stress tolerant endogenous pluripotent-like stem cells, and are involved in tissue repair. However, the significance of Muse cells in acute myocarditis has not been evaluated. In the present study, we counted Muse cells/area in biopsied myocardial tissue samples from 17 patients with fulminant myocarditis, and 6 with non-inflammatory myocardial disease as controls. Compared with controls, patients with fulminant myocarditis had significantly more Muse cells (p = 0.00042). Patients with mechanical circulatory support (p = 0.006) and myocardial degeneration (p = 0.023) had significantly more Muse cells than those without them. The Muse cell number was correlated with acute phase CK-MB level (ρ = 0.547, p = 0.029), indicating the severity of myocardial injury, and was also correlated with acute/recovery phase ratio of CK-MB (ρ = 0.585, p = 0.023) and cardiac troponin I (ρ = 0.498, p = 0.047) levels, indicating resilience of myocardial injury. In fulminant myocarditis, the Muse cell number was associated with the severity of clinical features in the acute phase, and also with the recovery from myocardial damage in the chronic phase. Endogenous Muse cells might be mobilized and accumulate to the myocardial tissues in fulminant myocarditis, and might participate in the repair of injured myocardium.