Nonviable human pre-implantation embryos as a source of stem cells for research and potential therapy.

Human embryonic stem cells are derived from the inner cell mass of the human blastocyst. Presumably normal (frozen/thawed) human preimplantation embryos that remain unused following assisted reproduction procedures have provided the main source of blastocysts for stem cell derivation. Alternatively, embryos have been generated from gametes donated for the unique purpose of in vitro fertilization, blastocyst culture, and stem cell isolation. This article describes two previously published methods--and the background to those methods--that allow the use of nonviable embryos excluded from transfer and cryopreservation as a source of stem cells. The first method is based on the observation that some blastomeres from embryos with abnormal division during the first 3-5 d in culture can continue very limited development in isolation. When aggregated in a chimaeric form, some of these blastomeres can contribute to the formation of normally organized blastocysts. Blastocysts so obtained provide a route to embryonic stem cells from otherwise nonviable embryos. Thus the inner cell masses of blastocysts obtained from trisomic embryos were placed on feeder cells and cultured for seven additional days, following which the resulting cell colonies were examined for chromosome content. The second method concerns embryos diagnosed with specific chromosome abnormalities many of which are incompatible with life. Some of these aneuploidies do not preclude development to the blastocyst stage in culture. A proportion of these cells were found to be disomic and the cultures were shown to express OCT-4, a molecular marker for pluripotent cells. This apparent correction of the trisomic state in some cells within the colonies suggests that embryos with cromosomal abnormalities incompatible with life may be another source of human embryonic stem cells.