Matter of the heart

Adult rat heart stem cells differentiate into cardiac myocytes and repair injured tissue | By Andrea Rinaldi

The prospect of improved regeneration or replacement of damaged tissues and organs is the main goal of stem cell research. Embryonic stem cells have been the focus of intense study in the past 2 decades, but the biology of the adult stem cells that persevere in mature tissues has been poorly understood. The presumption that adult tissues, such as the central nervous system, have low or no self-renewal potential has been challenged by the observation that these tissues host small groups of resident stem cells that may proliferate and repopulate injured areas. In the September 19 Cell, Antonio Beltrami and colleagues at the New York Medical College report that heart also contains adult stem cells, identifying rat myocytes having the properties of cardiac stem cells (Cell, 114:763-776, September 19, 2003).

Beltrami et al. analyzed the myocardium of adult Fisher rats for cells that expressed stem cell–related surface markers and identified small clusters of candidate cells that looked like primitive and early committed cells interspersed between well differentiated myocytes. The authors isolated, characterized, and cultured the cells and showed that they satisfy the properties expected for cardiac stem cells; they are self-renewing, clonogenic, and multipotent, giving rise to all the three main cardiac cell lineages (i.e., myocytes, smooth muscle cells, and endothelial vascular cells). When injected into ischemic hearts, these cells or their clonal progeny regenerated up to 70% of the infarcted myocardial wall of the left ventricle, including new blood-carrying vessels and contractile myocytes. The hearts treated with the putative cardiac stem cells exhibited functional improvement.

"The extraordinary clinical potential of myocardial regeneration makes the dissection of the biology of these cardiac stem cells a challenging and exciting endeavor," conclude the authors. The same team had previously shown that mice with experimentally induced myocardial infarcts recovered after bone marrow–derived stem cells were administered directly into the heart.

"The fact that the adult stem cells in this study can form endothelium, smooth muscle, and cardiac muscle is confounding, since these three cell types arise from three different cell lineages. Finally, if these cells exist and lie dormant in the heart, why do they not mobilize and divide in response to an injury?" questions Leslie Leinwand at the University of Colorado in an accompanying preview article.