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

Figures

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  FIGURE 1. The number of SSEA‐3 positive Muse cells/area measured in 5 randomly selected locations in the myocardial tissues of 17 patients with fulminant myocarditis (Cases 1–17), and 6 control patients with non‐inflammatory myocardium (Cases 18–23). Case 6, Case 10, and Case 17 are patients who died in the hospital. In the 17 fulminant myocarditis patients, the time from onset to biopsy was 5.5 ± 7.2 days (0–23 days, median 3 days). The number of Muse cells ranged from 8.0 ± 3.8 to 250.9 ± 68.6 cells/mm2 in the patients with fulminant myocarditis, and from 6.9 ± 3.6 to 15.9 ± 7.5 cells/mm2 in control subjects (data are mean ± SD).

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  FIGURE 2. Comparison of the number of Muse cells (mean value of measured cell number in 5 locations) in the myocardial tissues between 17 patients with fulminant myocarditis and 6 control patients. The Muse cell number was significantly higher in the myocardial tissues of patients with fulminant myocarditis compared with control subjects.

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  FIGURE 3. Representative findings of Muse cell localization in the biopsied myocardial tissues in 3 cases. (a) A 54‐year‐old female (Case 9 in Figure 1) with fulminant myocarditis. The patient developed a critical illness requiring mechanical ventilatory and circulatory support in addition to corticosteroid treatment. Histopathologic findings showed an inflammatory reaction with diffuse inflammatory cell infiltration. Muse cells highly accumulated at the site where inflammatory cell infiltration was strong. The number of Muse cells was 250.9 ± 68.6 cells/mm2. (b) A 54‐year‐old male (Case 10 in Figure 1) with fulminant myocarditis. This patient also required mechanical ventilatory and circulatory support. Although histopathologic findings of myocardial tissues showed diffuse inflammatory cell infiltration, only a small number of Muse cells was detected at the site of inflammation. Notably, the number of Muse cells (8.0 ± 3.0 cells/mm2) was the lowest among all 17 patients with fulminant myocarditis. (c) A 59‐year‐old male (Case 21 in Figure 1), who underwent a myocardial biopsy for suspected dilated cardiomyopathy. Histopathologic findings of the myocardial tissues showed a normal…

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  FIGURE 4. Comparison of Muse cell localization in the right ventricular myocardium between the acute phase biopsy specimen and the late‐phase autopsy specimen in a patient with fulminant myocarditis (58‐year‐old male; Case 17 in Figure 1), who died from a non‐cardiac cause. (a) In the acute phase biopsy specimen (3 days after onset), Muse cells accumulated mainly at the site of inflammation where many lymphocytes infiltrated. The mean number of Muse cells was 86.1 ± 11.4 cells/mm2. (b) In the autopsy heart (31 days after onset), Muse cells accumulated in the myocardium near the endocardium with and without inflammation. The mean Muse cell number was 89.8 ± 52.0 cells/mm2. The Muse cells are also sparsely located in the pericardium.