Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction

TLDR

Cell grafting or mobilizing endogenous cells is attractive for heart disease because adult myocardium has limited cardiomyocyte proliferation, yet it is unclear whether cardiac progenitors exist in the adult heart or whether they fuse with existing myocytes. The study used a Cre/Lox alphaMHC‑Cre/R26R system to demonstrate that cardiac progenitor cells differentiate in the heart with or without fusing to host cells. Adult heart‑derived cardiac progenitor cells expressing stem cell antigen‑1 were identified; they lack cardiac genes initially but can differentiate in vitro with 5′‑azacytidine via Bmpr1a, and when injected intravenously after ischemia/reperfusion, they home to injured myocardium.

Abstract

Potential repair by cell grafting or mobilizing endogenous cells holds particular attraction in heart disease, where the meager capacity for cardiomyocyte proliferation likely contributes to the irreversibility of heart failure. Whether cardiac progenitors exist in adult myocardium itself is unanswered, as is the question whether undifferentiated cardiac precursor cells merely fuse with preexisting myocytes. Here we report the existence of adult heart-derived cardiac progenitor cells expressing stem cell antigen-1. Initially, the cells express neither cardiac structural genes nor Nkx2.5 but differentiate in vitro in response to 5'-azacytidine, in part depending on Bmpr1a, a receptor for bone morphogenetic proteins. Given intravenously after ischemia/reperfusion, cardiac stem cell antigen 1 cells home to injured myocardium. By using a Cre/Lox donor/recipient pair (alphaMHC-Cre/R26R), differentiation was shown to occur roughly equally, with and without fusion to host cells.