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Embryonic stem cell

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Definition

Human embryonic stem cells in culture.
File:StemCellsDia.png
Pluripotent, embryonic stem cells originate as inner mass cells with in a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.

Embryonic stem cells (ESCs) are stem cells derived from the inner cell mass of a blastocyst, which is an early stage embryo - approximately 4 to 5 days old in humans - consisting of 50-150 cells. Embryonic stem cells are pluripotent, meaning they are able to grow (i.e. differentiate) into all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body as long as they are specified to do so. This characteristic property distinguishes embryonic stem cells from adult stem cells or progenitor cells, the latter two of which only have the capacity to form a limited number of different cell types. Because of their unique combined abilities of unlimited expansion and pluripotency, embryonic stem cells potentially are the ultimate source for regenerative medicine and tissue replacement after injury or disease. To date, no medical treatments have been successfully derived from embryonic stem cell research as the first human embryonic stem cell line was only first reported in 1998.

History

Embryonic stem cells were first derived from mouse embryos in 1981 by two independent research groups (Evans & Kaufman and Martin). The breakthrough in embryonic stem cell research came in November 1998 when a group led by James Thomson at the University of Wisconsin-Madison first developed a technique to isolate and grow the cells derived from human blastocysts. Normally, blastocyst-stage embryos that are left over after successful in vitro fertilization would not be used but be destroyed. Scientists are only allowed to use these discarded blastocysts after assessment by specialized committees that thoroughly check the research goals of these scientists. Of course, scientific research using those blastocysts may be conducted when it contributes to a better understanding of how to generate cells and tissues that can cure a patient's disease or be used to treat severe injuries. Currently, in the United States, scientific research is limited by a ban on the use of federal funds for research with embryonic stem cells derived after August 9th, 2001. Embryonic stem cell researchers are currently attempting to grow the cells in the laboratory (i.e. in culture flasks: "in vitro") beyond the first stages of cell development. It is important to make sure the embryonic stem cells are fully differentiated into the desired cell type (i.e. tissue) before they are transplanted into the patient, as undifferentiated embryonic stem cells may develop into a tumor after transplantation. Further more, scientists are trying to develop techniques to prevent rejection of implanted cells by the patient (i.e. host-versus-graft response).

One of the possibilities to prevent rejection is by creating embryonic stem cell clones that are genetically identical to the patient. This can be achieved by fusing an egg (oocyte), the nucleus (containing the genetic material: DNA) of which is removed, with a patient's cell. The fused cell produced (containing only the DNA of the patient) is allowed to grow to the size of a few tens of cells, and stem cells are then extracted. Because they are genetically compatible with the patient, the patient's immune system will not reject differentiated cells derived from these embryonic stem cells. More commonly, they are obtained for research purposes from uncloned blastocysts, such as those discarded from in vitro fertilization clinics. Such cells might be rejected if transplanted into a patient, as they do not contain identical genetic information. A possible solution for this is to derive as many well-characterized embryonic stem cell lines from different genetic and ethnic backgrounds and use the cell line that is most similar to the patient; treatment can then be tailored to the patient, minimizing the risk of rejection.


Controversial Aspects

Main article: Stem cell controversy

Stem cells are taken from a blastocyst, typically four or five days old, which is a hollow microscopic ball of about 150 cells , slightly larger than the period at the end of this sentence. After 14 days does a nervous system begins to develop and it is called an embryo.

Blastocysts, used by fertility clinics for in vitro fertilization, may be destroyed after a couple conceives a child, frozen (for future pregnancy attempts), or the couple can consent for them to be donated for medical research. But due to their own ethical dilemmas, many couples are unable to make a "dispensation decision" and as a result there are many frozen embryos in fertility clinics.] In a few cases, where couples have given permission for the embryos to be adopted, the embryos have been implanted and have grown to full-term babies (see Embryo adoption).

Developments

A major development in research came in May 2003, when researchers announced that they had successfully used embryonic stem cells to produce human egg cells. These egg cells could potentially be used in turn to produce new stem cells. If research and testing proves that artificially created egg cells could be a viable source for embryonic stem cells, they noted, then this would remove the necessity of starting a new embryonic stem cell line with the destruction of a blastocyst. Thus, the controversy over donating human egg cells and blastocysts could potentially be resolved, though a blastocyst would still be required to start each cycle.

The online edition of Nature Medicine published a study on January 23, 2005 which stated that the human embryonic stem cells available for federally funded research are contaminated with nonhuman molecules from the culture medium used to grow the cells, for example, mouse cells and other animal cells. The nonhuman cell-surface sialic acid can compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego.

A study was published in the online edition of Lancet Medical Journal on March 8, 2005 that detailed information about a new stem-cell line which was derived from human embryos under completely cell- and serum-free conditions. This event is significant because exposure of existing human embryonic stem-cell lines to live animal cells and serum risks contamination with pathogens that could lead to human health risks. After more than 6 months of undifferentiated proliferation, these cells retained the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem-cell lines. (Lancet Medical Journal)

Recently, in California, researchers have injected embryonic stem cells into mice as they developed in the womb. Upon maturing, it was found that some of the human ESCs had survived and two months after injection, the researchers found that the ESCs had undertaken "the characteristics of mouse cells" .

Scientists in Australia have grown human prostate in mice using embryonic stem cells. In a world first, the scientists combined human embryonic stem cells with mouse prostate cells, and used a mouse as the host to grow the human prostate. The researchers were able to show that it was also functioning as a human prostate. Doctors world wide would now be able to use this prostate as a model for studying prostate cancer and disease, and to produce future drugs.

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