Derivation of embryonic stem cells for cellular therapy: challenges and new strategies.

Cellular therapy is the replacement of unhealthy or damaged cells or tissues by new ones. Embryonic stem (ES) cells are undifferentiated cells that can generate all the cell types of the body, and therefore hold the potential to cure a broad range of diseases and injuries, ranging from diabetes, liver and heart diseases, to neurological diseases, such as Alzheimer's and Parkinson's diseases. The derivation of human ES (hES) cells has been a major step toward bringing ES cell research to therapy. However, there are several challenges to the advent of ES cell research to therapy. Among them, the derivation of hES cell lines devoid of animal contaminants, the maintenance of their normal karyotypes, their potentials to form tumors upon grafting, and the derivation of isogenic hES cell lines. Stringent ethical and political guidelines are also limiting the use of human embryos for research, thereby limiting progress in ES cell research. Recently, several investigators have devised protocols to derive hES cells free of feeder layer and animal serum, reported that some established cell lines remain stable overtime, pre-differentiated ES cells in vitro to circumvent the risk of tumor formation, and derived ES cell lines without destroying embryos. In this manuscript, we will review and discuss these developments that may unlock ES cell research and therapy.