Identification and characterization of stem cell-like SP cells in the post-natal myocardium

Abstract

The field of stem cell biology is continuously expanding, encompassing not only the traditional study of hematopoietic and fetal cells, but also the investigation of adult stem cells from a variety of tissue sources. The definitions and conventions adopted by the field of hematopoiesis have served as a framework for the more recent discoveries in adult stem cell biology. As such, stem cells are defined as immature progenitor cells capable of long term self-renewal and pluripotent differentiation. Using Fluorescence Activated Cell Sorter (FACS) analysis, a sub-population of distinct Hoechst dye-excluding cells, termed the 'side population' (SP), has been isolated from bone marrow (BM) (Goodell et al., 1996). These verapamil-sensitive cells are highly enriched in stem cell activity and have the capacity for lineage conversion. The potential for these cells to play a role in adult tissue maintenance and repair has been established in skeletal muscle, liver and brain. Here we report the existence of endogenous SP cells within the adult myocardium with similar but not identical characteristics to SPs from other adult tissues. These features include the capacity for cardiomyocyte differentiation and the expression of cell surface markers such as Sca-1 and CD34, but not hematopoietic lineage markers Gr-1, Mac-1 and CD4. Conversely, these cardiac-derived SP cells do not express the hematopoietic stem cell (HSC) markers c-kit and CD45. Furthermore, fusion but not transdifferentiation of these myocardial SP cells with skeletal myoblasts was observed. These results offer the first experimental evidence of a resident population of myocardial stem cells and suggest a potential for therapeutic applications in cardiac disease.