Identification of cardiac progenitors that survive in the ischemic human heart after ventricular myocyte death

摘要

Atypically-shaped cardiomyocytes (ACMs) are beating heart cells identified in the cultures of cardiomyocyte-removed fractions obtained from adult mouse hearts. Since ACMs spontaneously develop into beating cells in the absence of hormones or chemicals, these cells are likely to be a type of cardiac progenitors rather than stem cells. “Native ACMs” are found as small interstitial cells among ventricular myocytes that co-express cellular prion protein (PrP) and cardiac troponin T (cTnT) in mouse and human heart tissues. However, the endogenous behavior of human ACMs is unclear. In the present study, we demonstrate that PrP+ cTnT+ cells are present in the human heart tissue with myocardial infarction (MI). These cells were mainly found in the border of necrotic cardiomyocytes caused by infarcts and also in the hibernating myocardium subjected to the chronic ischemia. The ratio of PrP+ cTnT+ cells to the total cells observed in the normal heart tissue section of mouse and human was estimated to range from 0.3–0.8%. Notably, living human PrP+ cTnT+ cells were identified in the cultures obtained at pathological autopsy despite exposure to lethal ischemic conditions for hours after death. These findings suggest that ACMs could survive in the ischemic human heart and develop into a sub-population of cardiac myocytes.