An emerging consensus on cardiac regeneration

Abstract

Cardiac regeneration is a rapidly evolving and controversial field of research. The identification some 12 years ago of progenitor cells that reside within the heart spurred enthusiasm for cell-based regenerative therapies. However, recent evidence has called into question both the presence of a biologically important stem cell population in the heart and the ability of exogenously derived cells to promote regeneration through direct formation of new cardiomyocytes. Here, we discuss recent developments that suggest an emerging consensus on the ability of different cell types to regenerate the adult mammalian heart.

Figure 1

Genetic lineage tracing approaches to assess cardiomyocyte renewal. (a) Inducible α-myosin heavy chain (α-MHC) promoter–driven MerCreMer transgene crossed with a transgene reporter of LacZ-loxp-GFP (ZEG) that was used for labeling of adult cardiomyocytes (green cells, ~85% labeled) combined with ¹⁵N-thymidine labeling of DNA synthesis (red nuclei) followed by imaging mass spectrometry indicated a low rate of cardiomyocyte renewal of 1% per year from preexisting cardiomyocytes during normal aging (as examined in sham or control mice). After MI injury, ~3.2% new cardiomyocytes are generated from preexisting cardiomyocytes in the area adjacent to the infarct. (b) Inducible c-kit promoter–driven GFP labeling in the postnatal mouse heart shows multilineage potential of c-kit⁺ progenitor cells (green cells) with low ability to generate fibroblasts and smooth muscle cells and an even lower ability to generate cardiomyocytes (yearly rate calculated to be 0.05%). In contrast, a high preponderance of endothelial cells are derived from c-kit⁺ progenitors.