Differentiation and genetic manipulation of human embryonic stem cells and the analysis of the cardiovascular system

Abstract

Human embryonic stem (ES) cells are pluripotent cells derived from blastocyst-stage embryos. The cells are characterized by their self-renewal capability and by their ability to differentiate into a wide range of cell types. In vivo, injection of the human ES cells into immune-deficient mice generates teratomas harboring derivatives of all three embryonic germ layers. In vitro, spontaneous aggregation of human ES cells results in the formation of embryoid bodies (EBs) comprised of differentiated cells from the three embryonic germ layers. Induced differentiation of ES cells into specific subsets of cells may be generated by treatment with several growth factors. Cardiomyocytes and endothelial cells were among the tissue types identified in vitro, and one of the most dramatic examples for the differentiation of human ES cells is the formation of rhythmic contractions of EBs containing pulsing cardiac muscle cells. Cells of the cardiovascular system were characterized by many molecular markers and by their structural and functional properties. The ability to genetically manipulate human ES cells now allows for the purification of specific cell types. Human ES cells have tremendous value as an in vitro model to study embryonic differentiation and as a source of cells for cellular transplantation in various pathologies among them cardiovascular diseases.