Embryonic Stem Cells as a Model for Cardiac Development and Disease

This review highlights recent progress in the use of embryonic stem cell (ESC) systems for studying and treating cardiovascular disease. Although ESCs represent an in vitro system, they can provide a rich source of progenitor cells, and this has been exploited recently to identify novel precursors and to investigate the lineage relationships among various cell types that comprise the developing heart, including cardiac muscle, endothelium, and smooth muscle. ESCs grown in aggregates (embryoid bodies) recapitulate normal developmental programs. Since they can be grown under defined culture conditions, they have been used to systematically identify specific genes and signaling pathways that promote cardiogenesis. A major goal is to optimize the production of cardiac progenitors and differentiated cell types, and to test their ability to promote healing in transplant assays, for example post-infarction. While many challenges remain, the development of iPS technology provides a means to generate cells for autologous transplant and for investigating patient-specific disease mechanisms. The development of new techniques to derive cardiac derivatives in vitro from ESC or iPS sources, coupled with novel tissue-engineering approaches and a better understanding of how explanted cells can survive and integrate in host tissue, should have a significant impact on the development of both cell-based and pharmacological therapies for cardiovascular disease.