Research of cardiomyocyte precursors in adult rat heart

Abstract

Recent reports supported the existence of stem cells in adult hearts. However, phenotype and localization of these cells have not been completely described and it is unknown if cardiac regenerative potential differs from one subject to another. The aims of our work were to identify different populations of cardiac stem cells by the analysis of specific markers and to evaluate the expression variability of these markers in 12 adult rat hearts. The expression of CD9, taube nuss and nanog suggests the presence of stem cells from the earliest stages of embryogenesis in adult myocardium. Their different expression could be associated to the degree of stem cell differentiation. CD34 and c-Kit antibodies were used to detect stem cells committed to one or more specific tissue lineages and we found a strong immunoreactivity for CD34 exclusively in the endothelial cells and a low positivity for c-Kit in the interstitium and next to the vessels. Moreover, as c-Kit expression highly differed within all examined hearts, we suggest that cardiomyogenic potential is different among the various subjects. Undifferentiated cells with myogenic-committed phenotype expressing GATA-4 and nestin were found, respectively, in the interstitial and myocardial cells and in few interstitial cells. Therefore, the physiologic turn over of cardiomyocytes may occur in adult hearts as it has been shown in many others organs. The study of myogenic potential could be important to identify markers specific of stem cells in in vivo adult myocardium that may be used to purify these cells and evaluate their regenerative ability.

The phenotype and potential origin of nestin+cardiac myocyte-like cells following infarction

“…By contrast, the study by Oh et al 17identified a c-kit Ϫ population of cardiac progenitor cells that expressed Sca-1 and GATA4 and, following their injection in the ischemically damaged heart, differentiated to a cardiac myocyte. Several studies have reported the presence of nestinexpressing cells in the normal rat and mouse heart and the ischemically damaged human heart (2,6,11,25). Work from our laboratory (11) and Tomita et al (25) further demonstrated that these nestin-expressing cells exhibit a neural stem cell phenotype and are neural crest-derived.…”

“…neural crest-derived, and detected intercalated among cardiac myocytes in the normal rat and mouse heart (2,11,12,25). Following an ischemic insult, nestin-expressing neural stem cells residing in the viable myocardium migrated to the infarct region and were identified as a novel cellular substrate for de novo blood vessel formation (6,11,12).…”

Nestin+cells and healing the infarcted heart

“…Zaglia et al (63), Bellafiore et al (7), and Scobioala at al. (47) likewise identified nestin ϩ cells in the rodent heart expressing GATA4 and/or NKX2.5.…”

Nanog maintains human chondrocyte phenotype and function in vitro

“…Nanog expression is confined to the pregastrulation stage of development 25, 26. Recent findings suggest that Nanog is expressed in some adult stem cells of the skin, in papillary cells of the kidney, and in cardiac muscle where it may contribute to self‐renewal 27, 28. Masahiro et al reported that forced expression of Nanog maintained pluripotency of adult human bone marrow‐derived mesenchymal stem cells 29.…”