.Embryonic stem cells are derived from a four-to-five day embryo and
differentiate into derivatives of all three embryonic
germ layers. Methods are being developed that should overcome the problems associated with their use.Embryonic stem cells are grown in vitro under stringent conditions to maintain an undifferentiated state. Often the material used to support the cells is derived from animals. Consequently, the cells can incorporate N-glycolyl-neuraminic acid residues that are antigenic in humans. Methods have been developed that do not use a feeder and layer or animal serum and are thus free of animal contaminants.Some reports suggest that embryonic stem cells do not have a stable karyotype but others report stability. There is concern that the cells will be tumorgenic after
transplantation. To avoid tumorgenicity, embryonic cells could be encouraged to fully
differentiate in vitro or undifferentiated cells could be removed before transplantation.Immunogenicity of the cells is a major problem and recipients need to use immunosuppressant drugs. A somatic cell nuclear transfer method has been developed to produce isogenic cells. This method has been successfully used with human skin cells but the behaviour of the generated cells is not known.Protocols are being developed to alleviate some of the ethical and political issues surrounding embryonic stem cell transplantation. These protocols do not destroy the embryos. In mice a single-cell biopsy method has been described that does not destroy the embryo. This technique is very similar to Preimplanation genetic diagnosis. In the other technique, termed altered nucleur transfer, blastocysts are created that cannot grow because of a gene knockout. The cells retain the ability to differentiate. This technique has been described with a knockout of the CDX2 gene that is required for implantation. However, the use of a virus to inactivate the gene may pose problems to the patient or adversely affect the cells. There are no ethical concerns with the use of adult stem cells.Continued research should address these issues in order to establish stem cells asviable therapeutic agents.