Embryo stem cells

Zhang, X., Stojkovic, R, Przyborski, S. et al. 2006. Derivation of human embryonic stem cells from developing and arrested embryos. Stem Cells 24 2669-76. 

Cellular therapies in transplantation and cancer are based on specific cells separated or sorted from human blood, bone marrow, or cord blood by means of their specific cell surface markers or cell differentiation antigens, e.g., CD3, CD4, CD8, CD 14, CD 19, and CD34. For example, the CD34+ stem cells, especially those derived from human embryos, have the capacity to differentiate in culture to generate different somatic cells, e.g., liver cells, heart cells, neurons, etc. This exploding field of research is now termed regenerative medicine. 

Such cells are often classified on the basis of their original source as either embryonic or adult stem cells. As the name suggests, embryonic stem cells are derived from the early embryo, whereas adult stem cells are present in various tissues of the adult species. Much of the earlier work on embryonic stem cells was conducted using mouse embryos. Human embryonic stem cells were first isolated and cultured in the laboratory in 1998. Research on adult stem cells spans some four decades, with the discovery during the 1960s of haematopoietic stem cells in the bone marrow (Chapter 10). However, the exact distribution profile, role and ability to manipulate adult stem cells (particularly those outside of the bone marrow) are subjects of intense current research, and for which more questions remain than are answered. 

Embryonic stem cells are derived from pre-implant-stage human embryos, usually at the blastocyst stage (the blastocyst is a thin-walled hollow structure containing a cluster of cells, known as the inner cell mass, from which the embryo arises). These embryos are invariably ones initially generated as part of in vitro fertilization procedures but which are destined to be discarded, either due to poor quality or because they are in excess to requirement. There are an estimated 400 000 in vitro fertilization-produced embryos in frozen storage in the USA alone, of which some 2.8 per cent are likely to be discarded. 

A central role for neural stem cells in the development of the nervous system is becoming clear. During embryo-logical development, the nervous system originates from... 

Robin, C. and Dzierzak, E. Hematopoietic stem cell enrichment from the AGM region of the mouse embryo, Methods Mol. Med., 105, 257, 2005. 

Embryonic genome, random insertion of transgenes into, 12 454—459 Embryonic lethal, 12 460 Embryonic stem cells, gene transfer with, 12 457-459 Embryos... 

Totipotent stem cells are obtained from embryos that are less than 5 days old. These cells have the full potential to develop into another individual and every cell type. 

There are two general avenues for stem cell research pluripotent and multipotent stem cells. Pluripotent stem cells are obtained by two methods. One method is to harvest the clusters of cells from the blastocysts of human embryos. Another method is the isolation of pluripotent cells from fetuses in terminated pregnancies. Multipotent stem cells are derived from umbihcal cords or adult... 

A burning issue is the ethics of obtaining pluripotent stem cells from embryos and fetuses. The US government has acted on this issue and declared that federal funds for stem cell research have to meet certain criteria. It requires that funding will only be provided to research with stem cells obtained before August 9, 2001, as a cut-off date to limit research to preexisting stem cells. Refer to Section 11.7 for an ethical debate on stem cells. 

As discussed in Section 4.7, stem cells have the potential to treat medical conditions beyond the scope that can be offered by drugs alone. However, there are many scientific and ethical hurdles to overcome. On the scientific front, stem cell research activities will intensify over the next decade. These challenges can broadly be divided into (1) determining how to develop stem cells into specific tissues and (2) implanting these tissues into the body without rejection by the recipient s immune system. On the ethical front, it is expected that there will be more debates on the ethical issues of stem cell research. Most scientists consent to therapeutic cloning (stem cell research) but not reproductive cloning. The ethical issue of stem cell research concerns harvesting cells from embryos that are a few days old. This action destroys the embryos. Some questions are ... 

HEMATOPOIETIC STEM CELLS ALWAYS EMERGE AT THE CONTACT OE ENDOTHELIAL CELLS, BOTH IN THE YOLK SAC AND THEN IN EMBRYO PROPER... 

Gering M and Patient R (2005). Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos. Developmental Cell 8 389-400. 

North TE, de Bruijn MF and Stacy T, et al (2002). Runxl expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity 16(5) 661-72. 

Tavian M, Robin C, Coulombel L and Peault B (2001). The human embryo, but not its yolk sac, generates lympho-myeloid stem cells, mapping multipotent hematopoietic cell fate in intraembryonic mesoderm. Immunity 15 487-495. 

Evans, MJ. Kaufman, M. Establishment in cultme of pluripotential stem cells from mouse embryos. Nature 292,151 156 (1981). 

---