Ordinary skin cell may be converted into embryonic stem cells

The journal Nature published Sunday an article related to new embryonic stem cells research that has become a very promising field of study since 1964.

A team of researchers has discovered a way to convert an ordinary skin cell into embryonic-like stem cells, with the potential to grow batches of cells that can be directed to form any kind of tissue.

Embryonic stem cells (ES cells) are stem cells derived from the inner cell mass of an early stage embryo known as a blastocyst. Human embryos reach the blastocyst stage 4-5 days post fertilization, at which time they consist of 50-150 cells.

Stem cells were discovered from analysis of a type of cancer called a teratocarcinoma. Researchers noted that a single cell in teratocarcinomas could be isolated and remain undifferentiated in culture.Researchers learned that primordial embryonic germ cells (EG cells) could be cultured and stimulated to produce many different cell types.

Embryonic stem cells (ES cells) were first derived from mouse embryos in 1981 by Martin Evans and Matthew Kaufman and independently by Gail R. 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.

The online edition of Lancet Medical Journal on March 8, 2005 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.

On August 23, 2006 , the online edition of Nature scientific journal published a letter by Dr. Robert Lanza, medical director of Advanced Cell Technology in Worcester, MA, stating that his team had found a way to extract embryonic stem cells without destroying the actual embryo. This technical achievement would potentially enable scientists to work with new lines of embryonic stem cells derived using public funding. Federal funding is currently limited to research using embryonic stem cell lines derived prior to August 2001.

Professor Yamanaka had a recent breakthrough in which the skin cells of laboratory mice were genetically manipulated back to their embryonic state. This work was confirmed by two other groups, demonstrating that the addition of just 4 genes (Oct3/4, Sox3, Klf4, and Myc) could reprogram mouse skin cells into embryonic stem like cells. The ability to reproduce such findings are very important in science and the stem cell field, especially after Hwang Woo-Suk from Korea fabricated data, claiming to have generated human ES cells from cloned embryos. These cells produced by Yamanaka as well as the other laboratories demonstrated all the hallmarks of embryonic stem cells including the ability to form chimeric mice and contribute to the germ-line. One issue with this work is that the mice generated from these ES lines were prone to develop cancer due to the use of Myc, which is a known oncogene.

On 20th of November, 2007, two research teams, one of which was headed by Professor Yamanaka and the other by James Thompson announced a similar breakthrough with ordinary human skin cells that were transformed into batches of cells that look and act like embryonic stem cells. This may enable the generation of patient specific ES cell lines that could potentially be used for cell replacement therapies. In addition, this will allow the generation of ES cell lines from patients with a variety of genetic diseases and will provide invaluable models to study those diseases.

While this work is a huge accomplishment for science, there is still much work to be done before this technology can be used for the treatments of disease. First, the genes used to reprogram the skin cells into ES-like cells were added by the use of retroviruses that can cause mutations and lead to the risk of possible cancers. In addition, as shown with the mouse work, one of the genes used to reprogram, Myc, can also cause cancer. The group led by Thompson did not use Myc to reprogram and may not have this difficulty. Future work is aimed at attempting to reprogram without permanent genetic manipulation of the cells with viruses. This could be accomplished by either small molecules or other methodologies to express these reprogramming genes.

However, as a first indication that the induced pluripotent stem (iPS) cell technology can in rapid succession lead to new cures, it was used by a research team headed by Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge , Massachusetts , to cure mice of sickle cell anemia, as reported by Science journal's online edition on 6th of December.

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