Cardiac Stem Cells in the Postnatal Heart: Lessons from Development

Abstract

Heart development in mammals is followed by a postnatal decline in cell proliferation and cell renewal from stem cell populations. A better understanding of the developmental changes in cardiac microenvironments occurring during heart maturation will be informative regarding the loss of adult regenerative potential. We reevaluate the adult heart's mitotic potential and the reported adult cardiac stem cell populations, as these are two topics of ongoing debate. The heart's early capacity for cell proliferation driven by progenitors and reciprocal signalling is demonstrated throughout development. The mature heart architecture and environment may be more restrictive on niches that can host progenitor cells. The engraftment issues observed in cardiac stem cell therapy trials using exogenous stem cells may indicate a lack of supporting stem cell niches, while tissue injury adds to a hostile microenvironment for transplanted cells. Engraftment may be improved by preconditioning the cultured stem cells and modulating the microenvironment to host these cells. These prospective areas of further research would benefit from a better understanding of cardiac progenitor interactions with their microenvironment throughout development and may lead to enhanced cardiac niche support for stem cell therapy engraftment.

Figure 1

Summary of mouse heart development. (a) E3.5 preimplantation blastocyst stage showing pluripotent inner cell mass (ICM); (b) E6.5-gastrulating embryo showing mesoderm formation (arrows); (c) at E7.5, myocardial progenitor cells migrate to form the cardiac crescent; (d) at E8, the cardiac crescent fuses at the midline to form the early cardiac tube; (e) at E8.5, the cardiac tube forms a loop; (f) at E12.5–E15.5: the chambers undergo septation.

Figure 2

Summary of some of the cell differentiation stages with characteristic transcription factor markers (red) during embryonic development from zygote to cardiac and endothelial tissue.

Figure 3

Adult heart architecture with left ventricle wall cross section showing the myocardium organisation with the endocardium lining and epicardium outer layers. Cell types drawn are mature cardiomyocytes, cardiac fibroblasts in their collagen matrix, endothelial cells of the endocardium and capillaries, Purkinje fibres, and epithelial and connective tissue cells of the epicardium.

Figure 4

Diagram illustrating differentiation of pluripotent cells to cardiomyocytes. Markers for identification are shown for each step (red). ES or iPS cells differentiate towards mesoderm and cardiac mesoderm through cardiac progenitors and become mature, spontaneously contracting cardiomyocytes.