IDENTIFICATION OF C-KIT/CD105 AND ISL-1 CELLS IN HUMAN FETAL AND INFANT HEARTS

Abstract

During embryogenesis, the mammalian heart develops from a primitive heart tube, which derives from two bilateral primary heart fields located in the lateral plate mesoderm. Later on in the development process, the atrioventricular (A-V) canal and the sinu-atrial segment, at the venous pole, and the conotruncus, at the arterial pole, are added to the heart tube just prior to tube looping. In 2001 Waldo and colleagues and Kelly and colleagues demonstrated the presence of a secondary or anterior heart field in the ventral pharyngeal mesoderm. This region contains a pool of NKX2.5 and GATA-4 positive precardiac cells which migrate to the arterial pole of the primary heart tube. Isl-1 is a marker of the secondary heart field, and Isl-1+ fate-mapped cells can contribute to the right ventricle and outflow tract of the developing mouse heart. Most studies concerning the localization of cardiac precursor cells in the developing heart have been performed in mice or chicks, whereby the localization and identification of cardiac precursor cells in the human fetal and adult heart has been investigated only by Limana and colleagues, with their analysis limited to epicardium, and CD34+ or c-Kit+ cells. Isolation and characterization of adult human cardiac stem cells was characterized by the expression of c-Kit, the receptor for stem cell factor, and CD105, the regulatory component of the transforming growth factor-ß receptor complex important in angiogenesis and hematopoiesis. In view of this, in the present study, we analysed, by immunohistochemistry, the presence of c-Kit+/CD105+ and Isl-1+ cells in human normal hearts from infants and from fetuses at different gestational ages. We found that cells double positive for c-kit and CD105, and single positive for Isl-1 were present solely after the 18th week of gestation. Isl-1+ cells were localized also inside vessels, like non resident cells, in infant hearts.