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Human embryonic stem cell colony.
Human embryonic stem cell colony.
Pluripotent, embryonic stem cells originate as inner mass cells within 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.
Pluripotent, embryonic stem cells originate as inner mass cells within 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 (ES cells) are stem cells derived from the inner cell mass of an early stage embryo known as a blastocyst. Stem cells are cells found in most if not all multi-cellular Organisms. An embryo (from Greek:, plural, lit "that which grows" from en- "in" + bryein "to swell be full" is a multicellular The blastocyst is the structure formed in early Embryogenesis, after the formation of the Blastocoel, but before Implantation. Human embryos reach the blastocyst stage 4-5 days post fertilization, at which time they consist of 50-150 cells. Human fertilization is the union of a human egg and sperm, usually occurring in the Ampulla of the fallopian tube.

Embryonic Stem (ES) cells are able to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. In Developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized Cell type. A germ layer is a collection of cells formed during animal Embryogenesis. The ectoderm is the start of a tissue that covers the body surfaces Endoderm, (sometimes called Entoderm) is one of the Germ layers formed during animal Embryogenesis. One of the three Germ layers found in the Embryos of Animals more complex than Cnidarians making them Triploblastic. These include each of the more than 220 cell types in the adult body. The human body is the entire physical and mental structure of a Human Organism. Pluripotency distinguishes ES cells from multipotent progenitor cells found in the adult; these only form a limited number of cell types. Multipotent Progenitor cells can give rise to several other cell types but those types are limited in number The concept of a progenitor cell is difficult to define Like Stem cells, progenitor cells have a capacity to differentiate into a specific type of cell When given no stimuli for differentiation, (i. e. when grown in vitro), ES cells maintain pluripotency through multiple cell divisions. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism Cell division is a process by which a cell, called the parent cell divides into two or more cells called daughter cells. The presence of pluripotent adult stem cells remains a subject of scientific debate, however, research has demonstrated that pluripotent stem cells can be directly generated from adult fibroblast cultures. Adult stem cells are undifferentiated cells found throughout the body after embryonic development that divide to replenish dying cells and regenerate damaged A fibroblast is a type of cell that synthesizes and maintains the Extracellular matrix of many Animal tissues [1]

Because of their plasticity and potentially unlimited capacity for self-renewal, ES cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. However, to date, no approved medical treatments have been derived from embryonic stem cell research (ESCR). Adult stem cells and cord blood stems cells have thus far been the only stem cells used to successfully treat any diseases. Diseases treated by these non-embryonic stem cells include a number of blood and immune-system related genetic diseases, cancers, and disorders; juvenile diabetes; Parkinson's; blindness and spinal cord injuries. Besides the ethical problems of stem cell therapy (see stem cell controversy), there is a technical problem of graft-versus-host disease associated with allogeneic stem cell transplantation. Stem cell controversy is the ethical debate centered on research involving the creation usage and destruction of Human embryonic stem cells Some opponents of the research argue Graft-versus-host disease (GVHD is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize However, these problems associated with histocompatibility may be solved using autologous donor adult stem cells or via therapeutic cloning. Histocompatibility is the property of having the same or mostly the same Alleles of a set of Genes called the Major histocompatibility complex. In Biology, autologous refers to cells, tissues or even Proteins that are reimplanted in the same individual as they come from Adult stem cells are undifferentiated cells found throughout the body after embryonic development that divide to replenish dying cells and regenerate damaged Genetics and Developmental biology, somatic cell nuclear transfer ( SCNT) is a Laboratory technique for creating an Ovum with a donor

Contents

Research history and developments

Isolation and in vitro culture

Stem cells were discovered from analysis of a type of cancer called a teratocarcinoma. A germ cell tumor ( GCT) is a Neoplasm derived from Germ cells Germ cells normally occur inside the gonads ( Ovary and Testis) In 1964, researchers noted that a single cell in teratocarcinomas could be isolated and remain undifferentiated in culture. These types of stem cells became known as embryonic carcinoma cells (EC cells). [2] 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. Sir Martin John Evans FRS (born 1 January 1941) is a British scientist credited with discovering how to culture Embryonic stem In 1981 Matthew H Kaufman and Martin Evans at the University of Cambridge in England and Gail R Professor Gail R Martin, is in charge of the developmental biology program at the University of California San Francisco. Gail R. Martin is credited with coining the term 'Embryonic Stem Cell'. [3][4] 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. James Alexander Thomson (born December 20 1958, at Oak Park, Illinois, USA) is an American developmental biologist [5]

Production of male gametes

Researchers at the Whitehead Institute announced in 2003 that they had successfully used embryonic stem cells to produce haploid, male gametes. Founded in 1982, the Whitehead Institute for Biomedical Research is a non-profit research and teaching institution located in Cambridge Massachusetts. "Haplo" redirects here For the fictional character see The Death Gate Cycle. A gamete (from Ancient Greek γαμέτης; translated gamete = wife gametes = husband is a cell that fuses with another gamete They found embryonic stem cells that had begun to differentiate into embryonic germ cells and then further differentiated into the male haploid cells. Germ cells are progenitors of the Gametes. These singled out cells move through the gut to the developing Gonads and undergo mitotic proliferation followed When injected into oocytes, these haploid cells restored the somatic diploid complement of chromosomes and formed blastocysts in vitro. An oocyte, ovocyte, or rarely ocyte, is a female Gametocyte or Germ cell involved in reproduction. "Haplo" redirects here For the fictional character see The Death Gate Cycle. A chromosome is an organized structure of DNA and Protein that is found in cells. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism [6]

Contamination by reagents used in cell culture

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. Events 393 - Roman Emperor Theodosius I proclaims his nine year old son Honorius co-emperor Year 2005 ( MMV) was a Common year starting on Saturday (link displays full calendar of the Gregorian calendar. 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. Sialic acid is a generic term for the N - or O -substituted derivatives of Neuraminic acid, a Monosaccharide with a nine- Carbon backbone The University of California San Diego (popularly known as UC San Diego or UCSD) is a public Research university in San Diego, California [7]

However, a study published in 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. Events 1618 - Johannes Kepler discovers the third law of planetary motion. Year 2005 ( MMV) was a Common year starting on Saturday (link displays full calendar of the Gregorian calendar. 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. A teratoma is a type of neoplasm. The word teratoma comes from Greek and means roughly "monstrous tumor" These properties were also successfully maintained (for more than 30 passages) with the established stem cell lines. [8]

Reducing donor-host rejection

There is also ongoing research to reduce the potential for rejection of the differentiated cells derived from ES cells once researchers are capable of creating an approved therapy from ES cell research. One of the possibilities to prevent rejection is by creating embryonic stem cells that are genetically identical to the patient via therapeutic cloning. Genetics and Developmental biology, somatic cell nuclear transfer ( SCNT) is a Laboratory technique for creating an Ovum with a donor

An alternative solution for rejection by the patient to therapies derived from non-cloned ES cells 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.

Potential method for new cell line derivation

On August 23, 2006, the online edition of Nature scientific journal published a letter by Dr. Nature is a prominent Scientific journal, first published on 4 November 1869 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. Robert Lanza is Chief Scientific Officer of Advanced Cell Technology (ACT and Adjunct Professor at the Institute for Regenerative Medicine Wake Forest University Advanced Cell Technology (ACT a Biotechnology company formed in 1994 is involved with therapeutic cloning and the cloning of animals [9] 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.

See also: Induced pluripotent stem cell

Professor Yamanaka had a recent breakthrough[10] in which the skin cells of laboratory mice were genetically manipulated back to their embryonic state. Induced pluripotent stem cells Unfortunately one of the four genes used (namely c-Myc is Oncogenic, and 20% of the chimeric mice developed cancer This work was confirmed by two other groups, demonstrating that the addition of just 4 genes (Oct3/4, Sox2, Klf4, and c-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. Hwang Woo-Suk ( Korean: 황우석 born 29 January 1953 is a South Korean. 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 Thomson[11] 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, although recent research by professor Yamanaka's research group has made advances in avoiding this particular problem. [12]

In addition, as shown with the mouse work, one of the genes used to reprogram, Myc, can also cause cancer. The group led by Thomson 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. Induced pluripotent stem cells Unfortunately one of the four genes used (namely c-Myc is Oncogenic, and 20% of the chimeric mice developed cancer Rudolf Jaenisch (1942-) is a German pioneer of transgenic science, in which an animal’s genetic makeup is altered Founded in 1982, the Whitehead Institute for Biomedical Research is a non-profit research and teaching institution located in Cambridge Massachusetts. The city of Cambridge (ˈkeɪmbrɪdʒ is a university town and the administrative centre of the county of Cambridgeshire, England The Commonwealth of Massachusetts ( is a state located in the New England region of the northeastern United States. Sickle-cell disease or sickle-cell anaemia (or anemia) is a Blood disorder characterized by Red blood cells that assume an abnormal rigid Science is the Academic journal of the American Association for the Advancement of Science and is considered one of the world's most prestigious Scientific [13]

On January 16, 2008, a California based company, Stemagen, announced that they had created the first mature cloned human embryos from single skin cells taken from adults. These embryos can be harvested for patient matching embryonic stem cells. [14]

References

  1. ^ Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (August 25, 2006). "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors". Cell. Cell is a biweekly peer-reviewed scientific journal which publishes novel research in any area of experimental biology that is significant outside its field  
  2. ^ Andrews P, Matin M, Bahrami A, Damjanov I, Gokhale P, Draper J (2005). "Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the same coin. ". Biochem Soc Trans 33 (Pt 6): 1526-30. PMID 16246161.  
  3. ^ Evans M, Kaufman M (1981). "Establishment in culture of pluripotential cells from mouse embryos. ". Nature 292 (5819): 154-6. doi:10.1038/292154a0. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 7242681.  
  4. ^ Martin G (1981). "Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. ". Proc Natl Acad Sci U S A 78 (12): 7634-8. doi:10.1073/pnas.78.12.7634. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 6950406.  
  5. ^ Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V, Jones J (1998). "Embryonic stem cell lines derived from human blastocysts. ". Science 282 (5391): 1145-7. doi:10.1126/science.282.5391.1145. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 9804556.  
  6. ^ "Derivation of embryonic germ cells and male gametes from embryonic stem cells" (January 8, 2004). Nature 427: 148-154. Nature is a prominent Scientific journal, first published on 4 November 1869 doi:10.1038/nature02247. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
  7. ^ Access to articles : Nature Medicine
  8. ^ Lancet Medical Journal
  9. ^ Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R. (2006). "Human embryonic stem cell lines derived from single blastomeres. ". Nature 444 (7118): 481-5. PMID 16929302.  
  10. ^ "Human stem cells may be produced without embryos ‘within months’", Zangani, July 17, 2007.  
  11. ^ "Embryonic stem cells made without embryos", Reuters, November 21, 2007. This article is primarily about Reuters prior to its 2008 merger with Thomson  
  12. ^ "Researchers get closer to safe stem cell treatments", AFP, February 14, 2008.  
  13. ^ Rick Weiss. "Scientists Cure Mice Of Sickle Cell Using Stem Cell Technique: New Approach Is From Skin, Not Embryos", Washington Post, December 7, 2007, pp. The Washington Post is the largest and most circulated Newspaper in Washington D  A02.  
  14. ^ Helen Briggs. "US team makes embryo clone of men", BBC, January 17, 2008, pp.  A01.  

External links

See also

The National Academies called for the establishment of Embryonic Stem Cell Research Oversight (ESCRO Committees in its 2005 Guidelines for Human Embryonic Stem Cell Research to manage Embryoid bodies are Aggregates of cells derived from Embryonic stem cells, and have been studied for years with mouse embryonic stem cells Stem cell controversy is the ethical debate centered on research involving the creation usage and destruction of Human embryonic stem cells Some opponents of the research argue
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