Embryonic stem cells in cardiac repair and regeneration

Abstract

Cell transplantation is a subject of fast-growing research with a potential of a therapeutic approach for the treatment of heart diseases. Clinical applications require preparation of large number of donor cells. Stem cell studies published to date demonstrate that scientists have not reached the general consensus to use an optimal cell type for better cardiac repair and regeneration. We used embryonic stem (ES) cells and their released factors for cardiac repair and regeneration. The major concern of cardiac regeneration with stem cells includes engraftment, differentiation, and teratoma formation after ES cell transplantation. Our current knowledge of ES cell transplantation in the heart is very limited. This review discusses the use of various growth factors to enhance ES cells engraftment and differentiation, as well as the issue of teratoma formation.

FIG. 1.

Left panel (A) demonstrates a general scheme outlining differentiation of cardiac myocytes from the mouse ES-EB in vitro. Right panel (B) shows that transplanted ES cells in the infarcted mouse heart can engraft and differentiate into heart-cell types, as well as inhibit adverse cardiac remodeling and improve heart function.

FIG. 2.

Left panel demonstrates that transplanted undifferentiated ES cells (yellow, 30K) in the peri-infarcted (red and blue) and infarcted (blue) mouse heart can easily spread out in the cardiac microenvironment (dispersed small yellow dots) and differentiate into heart-cell types (ECs, endothelial cells; SMCs, smooth muscle cells; and cardiac myocytes). In contrast, the right panel demonstrates that transplanted ES cells (>100K) may localize to the needle-track area of injection (thick yellow dot) and be exposed to the internal ES cell microenvironment (dark blue area inside the yellow thick dot) and later develop a teratoma (dark blue area). The teratoma contains most of differentiated body-cell types (different colors represent various cell types). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article at www.liebertonline.com/ars).