C-kit cardiac progenitor cells: What is their potential?

Abstract

The very interesting paper by Tallini et al. (1) confirms our suggestion [derived from the study (2) of cardiospheres' formation by cardiovascular precursors (CPs) isolated from the heart of embryonic, fetal, neonatal, and adult transgenic mice expressing GFP under the control of the c-kit promoter] that c-kit expression identifies in the heart CPs, differentiating into endothelial, cardiac, and smooth muscle cells. On the basis of results obtained in adult hearts after cryoablation, Tallini et al. suggest that c-kit expression is associated with fibrous and vascular infarct repair but not with de novo myogenesis from c-kit+ CPs. They conclude that the increased c-kit expression in differentiated cardiomyocytes, in the injury border zone, could be the result of c-kit reexpression in committed myocytes (1). However, Hsieh et al. (3), using a genetic fate pulse-labeling approach, strongly evidenced that CPs contribute to the replacement of adult mammalian cardiomyocytes after injury, although not significantly to their renewal during normal aging. Although this study did not address the origin of the progenitors, heart-resident CPs appear to be the most likely source (4). The relationship between the various resident CPs so far described and their role in normal cardiac homeostasis, as well as their response to injury and the potential contribution of cardiomyocyte de-differentiation, await clarification. The apparently conflicting results will require careful assessment of these multiple hypothesis including the possibility, recently suggested by Bergmann et al (5), of the potential cell cycle reentry by some cardiomyocytes to resume DNA synthesis and mitosis.