The Derivation of Human Embryonic Stem Cell Lines from PGD Embryos

Embryonic stem cells are pluripotent cells that are derived from the early stage embryo (the blastocyst stage). Embryonic stem cells are the only cells that have the ability to provide an unlimited source of daughter cells and can differentiate into virtually any cell of the body.

Human embryonic stem cell lines have previously been derived from supernumerary embryos donated by couples undergoing IVF treatment. Thomson was the second in the world to isolate human embryonic stem cells. We derived six human embryonic stem cell lines, which are registered with the National Institute of Health and are eligible for American federal funding for research. We are widely distributing our cell lines to many researchers worldwide.

The key features of human embryonic stem cells are their potential of unlimited proliferation in culture, and their ability to differentiate into a large variety of somatic cells of the body. Our group was the first to show this capability in culture (1). Our results, and the results of other groups show that human embryonic stem cells can differentiate in culture into nerve cells, blood cells, pancreatic cells that secrete insulin, heart muscle cells, and others. Given the key properties of human embryonic stem cells, they are expected to have far reaching applications in basic scientific research, development of new drugs, and may serve as an unlimited donor source of cells for transplantation.

Embryonic stem cells will be recovered from human blastocysts donated to stem cell research by couples that have undergone preimplantation genetic diagnosis (PGD) of their embryos during IVF. In PGD, a number of embryos are generated by routine IVF, and cellular material is then taken as a biopsy from early human embryos that have been cultured in vitro. Embryos that are found to be genetically normal are selectively transferred to the uterus. A portion of the tested embryos will not have a diagnosis or will be found to contain specific genetic mutations or chromosomal aberrations. After discussion with the couple and subjected to their consent, these embryos will not be implanted in the potential mother for the purposes of pregnancy. It should be noted that in cases of uncertain diagnosis the couples may elect to transfer the embryos and perform prenatal diagnosis and pregnancy termination in cases where the fetus is found to be affected. Otherwise, the affected embryos or those without a certain diagnosis are truly surplus embryos that are routinely discarded. We wish to derive human embryonic stem cell lines from these embryos, since they will contain a specific mutation or chromosomal aberration that will be of interest to the research community. The genetically abnormal stem cells, that will be derived from these PGD-tested embryos, will be useful tools for the investigation of early development, cell function, disease progression, and for the efficacy or toxicity of drug therapies for the genetic abnormalities that they will carry. Derivation of human ES cell lines that harbor a specific gene defect will have great importance in the study and development of treatments for certain inheritable disorders. In addition, they may be employed for the development of gene therapy strategies designed for potential treatment of specific inherited disorders.

It should be stressed that the embryos that will be recruited for this study would have been discarded in any event, and would not have been implanted to produce a child. The embryos, while precious, will contain or will be suspected to contain undesired chromosomal or single gene defects, and will not have been deemed acceptable for transfer by the couple undergoing IVF. By contrast, these embryos, while not suitable for the purposes of producing healthy offspring, are valuable to stem cell research as key tools for the study of specific human disorders, therapies, for the investigation of early human development, in the derivation of new medications to treat diseases, and possibly to correct genetic defects. Rather than simply discarding and destroying the stem cells within these faulty embryos, they will be salvaged and utilized in the derivation of new disease-specific human embryonic stem cell lines.