Embryonic stem cell
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 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 when given sufficient and necessary stimulation for a specific cell type. When given no stimuli for differentiation, ESCs will continue to divide in vitro and each daughter cell will remain pluripotent. The pluripotency of ESCs distinguishes them from adult stem cells or progenitor cells, the latter two only having the capacity to form a more limited number of different cell types.
Because of their unique combined abilities of unlimited expansion and pluripotency, embryonic stem cells are a potential source for regenerative medicine and tissue replacement after injury or disease. To date, no approved medical treatments have been derived from embryonic stem cell research. This is not unusual for a new medical research field; in this case, the first human embryonic stem cell line was only reported in 1998.
Research history and developments
Embryonic stem cells were first derived from mouse embryos in 1981 by two independent research groups (Evans & Kaufman and Martin). A breakthrough in human 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 when derived from human blastocysts.
Researchers at the Whitehead Institute announced in 2003 that they had successfully used embryonic stem cells to produce haploid, male gametes. They found embryonic stem cells that had begun to differentiate into embryonic germ cells and then further differentiated into the male haploid cells. When injected into oocytes, these haploid cells restored the somatic diploid complement of chromosomes and formed blastocysts in vitro.[1]
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 non-human molecules from the culture medium used to grow the cells. It is a common technique to use mouse cells and other animal cells to maintain the pluripotency of actively dividing stem cells. The problem was discovered when non-human sialic acid in the growth media was found to compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego[2].
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. After more than 6 months of undifferentiated proliferation, these cells demonstrated 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 HESCs had undertaken "the characteristics of mouse cells" [3].
Scientists in Australia have grown human prostate tissue in mice through the use of ESCs. The research involved combining human ESCs with mouse prostate cells, and then using a mouse as the host to grow the human prostate. The researchers were able to show the resulting tissue was also functional as a human prostate. This work may enable medical researchers to use a prostate derived in this manner as a model for studying prostate cancer and disease and analysis of future prostate-related drugs.
There is also ongoing research to reduce the potential for rejection of the differentiated cells derived from ESCs once researchers are capable of creating an approved therapy from ESC research. One of the possibilities to prevent rejection is by creating embryonic stem cells 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 the nucleus from another of the patient's cells. The fused cell produced, similar to a zygote, is allowed to begin dividing based on the instructions available within the materials originating in the oocyte cytoplasm. At an early blastocyte stage, embryonic stem cells can be extracted. Because they are genetically identical to the patient, the patient's immune system will not reject differentiated cells derived from these embryonic stem cells. An alternative solution for rejection by the patient to therapies derived from non-cloned ESCs is to derive many well-characterized ES cell lines from different genetic 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.
New Technique In Extraction of Cells
In a Thursday, August 24th, 2006 article in the online edition of Nature Magazine. An article with a paper by Dr. Robert Lanza (medical director of Advanced Cell Technology in Worcester, Mass) that his team, who headed the research, had found a way to extract stem cells without destroying the actual embryo. This technical achievement may enable scientists to circumvent the ban on federal funding of stem cell research. There are currently significant restrictions on federal funding of stem cell research, instituted by George W. Bush, which he had derived from a moral belief that destroying the embryo is murder and is associated with abortion.
In the experiments, Lanaza's team used a single-cell biopsy technique to pluck out one cell when the embryo was at the 8-to-10-cell stage. This is the same stage used for pre-implantation genetic diagnosis. Excising a cell at this point doesn't interfere with the embryo's development. Using this method, Lanza and his team managed to get two stable human embryonic stem cell lines that behaved like conventional embryonic stem cell lines. The approach described here does not involve the destruction of an embryo, nor does the biopsied cell ever develop into an embryo at any point. This new technique has not made its way to congressional debate or bills as of yet, due to it being newly discovered.
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