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what are STEM CELLS????
Stem cells are cells found in most, if not all, multi-cellular organisms.
They are characterized by the ability to renew themselves through mitotic cell division and differentiating into a diverse range of specialized cell types.
Research in the stem cell field grew out of findings by Canadian scientists Ernest A. McCulloch and James E.
Till in the 1960s the two broad types of mammalian stem cells are: embryonic stem cells that are isolated from the inner cell mass of blastocysts, and adult stem cells that are found in adult tissues.
In a developing embryo, stem cells can differentiate into all of the specialized embryonic tissues.
In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of regenerative organs, such as blood, skin or intestinal tissues.
Stem cells can now be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture.
Highly plastic adult stem cells from a variety of sources, including umbilical cord blood and bone marrow, are routinely used in medical therapies. Embryonic cell lines and autologous embryonic stem cells generated through therapeutic cloning have also been proposed as promising candidates for future therapies.
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The classical definition of a stem cell requires that it possess two properties:
* Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
* Potency - the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent - to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells.
Potency definitions
Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[4]
* Totipotent (a.k.a omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable, organism.[4] These cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.[citation needed]
* Pluripotent stem cells are the descendants of totipotent cells and can differentiate into nearly all cells,[4] i.e. cells derived from any of the three germ layers.[5]
* Multipotent stem cells can differentiate into a number of cells, but only those of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).[4]
* Oligopotent stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem cells.[4]
* Unipotent cells can produce only one cell type, their own,[4] but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells).
Identification
The practical definition of a stem cell is the functional definition - the ability to regenerate tissue over a lifetime. For example, the gold standard test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.
Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, where single cells are characterized by their ability to differentiate and self-renew.[6][7] As well, stem cells can be isolated based on a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells.
Embryonic
Main article: Embryonic stem cell
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos.[8] A blastocyst is an early stage embryo—approximately four to five days old in humans and consisting of 50–150 cells. ES cells are pluripotent and give rise during development to 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. They do not contribute to the extra-embryonic membranes or the placenta.
Nearly all research to date has taken place using mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia Inhibitory Factor (LIF).[9] Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic Fibroblast Growth Factor (bFGF or FGF-2).[10] Without optimal culture conditions or genetic manipulation,[11] embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the presence of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and SOX2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[12] The cell surface antigens most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[13]
After nearly ten years of research[14], there are no approved treatments or human trials using embryonic stem cells. ES cells, being pluripotent cells, require specific signals for correct differentiation - if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[15] Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.
Adult
Main article: Adult stem cell
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The term adult stem cell refers to any cell which is found in a developed organism that has two properties: the ability to divide and create another cell like itself and also divide and create a cell more differentiated than itself. Also known as somatic (from Greek Σωματικóς, "of the body") stem cells and germline (giving rise to gametes) stem cells, they can be found in children, as well as adults.[16]
Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood.[17] A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.[18] In mice, pluripotent stem cells are directly generated from adult fibroblast cultures. Unfortunately, many mice don't live long with stem cell organs [19]
Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.).[20][21]
Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants.[22] Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.[23] The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, because in some instances adult stem cells can be obtained from the intended recipient, (an autograft) the risk of rejection is essentially non-existent in these situations. Consequently, more US government funding is being provided for adult stem cell research.[24]
Lineage
Main article: Stem cell line
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[25]
An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals dpp and adherens junctions that prevent germarium stem cells from differentiating.[26][27]
Main article: Induced Pluripotent Stem Cell
The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include several transcription factors including the oncogene c-Myc. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent.[28] However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy.
Treatments
Main article: Stem cell treatments
Medical researchers believe that stem cell therapy has the potential to dramatically change the treatment of human disease. A number of adult stem cell therapies already exist, particularly bone marrow transplants that are used to treat leukemia.[29] In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety of diseases including cancer, Parkinson's disease, spinal cord injuries, Amyotrophic lateral sclerosis, multiple sclerosis, and muscle damage, amongst a number of other impairments and conditions.[30][31] However, there still exists a great deal of social and scientific uncertainty surrounding stem cell research, which could possibly be overcome through public debate and future research, and further education of the public.
Stem cells, however, are already used extensively in research, and some scientists do not see cell therapy as the first goal of the research, but see the investigation of stem cells as a goal worthy in itself.[32]
Controversy surrounding research
Main article: Stem cell controversy
There exists a widespread controversy over human embryonic stem cell research that emanates from the techniques used in the creation and usage of stem cells. Human embryonic stem cell research is controversial because, with the present state of technology, starting a stem cell line requires the destruction of a human embryo and/or therapeutic cloning. However, recently, it has been shown in principle that adult stem cell lines can be manipulated to generate embryonic-like stem cell lines using a single-cell biopsy similar to that used in preimplantation genetic diagnosis that may allow stem cell creation without embryonic destruction.[33] It is not the entire field of stem cell research, but the specific field of human embryonic stem cell research that is at the centre of an ethical debate.
Opponents of the research argue that embryonic stem cell technologies are a slippery slope to reproductive cloning and can fundamentally devalue human life. Those in the pro-life movement argue that a human embryo is a human life and is therefore entitled to protection.
Contrarily, supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It is also noted that excess embryos created for in vitro fertilization could be donated with consent and used for the research.
The ensuing debate has prompted authorities around the world to seek regulatory frameworks and highlighted the fact that stem cell research represents a social and ethical challenge.
Key research events
* 1908 - The term "stem cell" was proposed for scientific use by the Russian histologist Alexander Maksimov (1874–1928) at congress of hematologic society in Berlin. It postulated existence of haematopoietic stem cells.
* 1960s - Joseph Altman and Gopal Das present scientific evidence of adult neurogenesis, ongoing stem cell activity in the brain; their reports contradict Cajal's "no new neurons" dogma and are largely ignored.
* 1963 - McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow.
* 1968 - Bone marrow transplant between two siblings successfully treats SCID.
* 1978 - Haematopoietic stem cells are discovered in human cord blood.
* 1981 - Mouse embryonic stem cells are derived from the inner cell mass by scientists Martin Evans, Matthew Kaufman, and Gail R. Martin. Gail Martin is attributed for coining the term "Embryonic Stem Cell".
* 1992 - Neural stem cells are cultured in vitro as neurospheres.
* 1997 - Leukemia is shown to originate from a haematopoietic stem cell, the first direct evidence for cancer stem cells.
* 1998 - James Thomson and coworkers derive the first human embryonic stem cell line at the University of Wisconsin-Madison.[34]
* 2000s - Several reports of adult stem cell plasticity are published.
* 2001 - Scientists at Advanced Cell Technology clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.[35]
* 2003 - Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth.[36]
* 2004–2005 - Korean researcher Hwang Woo-Suk claims to have created several human embryonic stem cell lines from unfertilised human oocytes. The lines were later shown to be fabricated.
* 2005 - Researchers at Kingston University in England claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical cord blood. The group claims these cells are able to differentiate into more types of tissue than adult stem cells.
* August 2006 - Rat Induced pluripotent stem cells: the journal Cell publishes Kazutoshi Takahashi and Shinya Yamanaka.
Takahashi K, Yamanaka S (Aug 2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors". Cell 126 (4): 663–76. doi:10.1016/j.cell.2006.07.024. PMID 16904174. http://www.cell.com/content/article/fulltext?uid=PIIS0092867406009767.
* October 2006 - Scientists at Newcastle University in England create the first ever artificial liver cells using umbilical cord blood stem cells.[37][38]
* January 2007 - Scientists at Wake Forest University led by Dr. Anthony Atala and Harvard University report discovery of a new type of stem cell in amniotic fluid.[39] This may potentially provide an alternative to embryonic stem cells for use in research and therapy.[40]
* June 2007 - Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.[41] In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer[42]
* October 2007 - Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.[43]
* November 2007 - Human Induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors",[44] and in Science by Junying Yu, et al., from the research group of James Thomson, "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells":[45] pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of tumorigenesis due to c-myc and retroviral gene transfer remains to be determined.
* January 2008 - Robert Lanza and colleagues at Advanced Cell Technology and UCSF create the first human embryonic stem cells without destruction of the embryo[46]
* January 2008 - Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts[47]
* February 2008 - Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach: these iPS cells seem to be more similar to embryonic stem cells than the previous developed iPS cells and not tumorigenic, moreover genes that are required for iPS cells do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques. [48][49]
* March 2008-The first published study of successful cartilage regeneration in the human knee using autologous adult mesenchymal stem cells is published by Clinicians from Regenerative Sciences[50]
* October 2008 - Sabine Conrad and colleagues at Tübingen, Germany generate pluripotent stem cells from spermatogonial cells of adult human testis by culturing the cells in vitro under leukemia inhibitory factor (LIF) supplementation. [51]
* 30 October 2008 - Embryonic-like stem cells from a single human hair.[52]
Funding & policy debate in the US
* 1993 - As per the National Institutes of Health Revitalization Act, Congress and President Bill Clinton give the NIH direct authority to fund human embryo research for the first time.[53]
* 1995 - The U.S. Congress passes an appropriations bill attached to which is a rider, the Dickey Amendment which prohibited federally appropriated funds to be used for research where human embryos would be either created or destroyed. President Clinton signs the bill into law. This predates the creation of the first human embryonic stem cell lines.
* 1999 - After the creation of the first human embryonic stem cell lines in 1998 by James Thomson of the University of Wisconsin, Harriet Rabb, the top lawyer at the Department of Health and Human Services, releases a legal opinion that would set the course for Clinton Administration policy. Federal funds, obviously, could not be used to derive stem cell lines (because derivation involves embryo destruction). However, she concludes that because human embryonic stem cells "are not a human embryo within the statutory definition," the Dickey-Wicker Amendment does not apply to them. The NIH was therefore free to give federal funding to experiments involving the cells themselves. President Clinton strongly endorses the new guidelines, noting that human embryonic stem cell research promised "potentially staggering benefits." And with the guidelines in place, the NIH begins accepting grant proposals from scientists.[53]
* 02 November, 2004 - California voters approve Proposition 71, which provides $3 billion in state funds over ten years to human embryonic stem cell research.
* 2001–2006 - U.S. President George W. Bush signs an executive order which restricts federally-funded stem cell research on embryonic stem cells to the already derived cell lines. He supports federal funding for embryonic stem cell research on the already existing lines of approximately $100 million and $250 million for research on adult and animal stem cells.
* 5 May, 2006 - Senator Rick Santorum introduces bill number S. 2754, or the Alternative Pluripotent Stem Cell Therapies Enhancement Act, into the U.S. Senate.
* 18 July, 2006 - The U.S. Senate passes the Stem Cell Research Enhancement Act H.R. 810 and votes down Senator Santorum's S. 2754.
* 19 July, 2006 - President George W. Bush vetoes H.R. 810 (Stem Cell Research Enhancement Act), a bill that would have reversed the Dickey Amendment which made it illegal for federal money to be used for research where stem cells are derived from the destruction of an embryo.
* 07 November, 2006 - The people of the U.S. state of Missouri passed Amendment 2, which allows usage of any stem cell research and therapy allowed under federal law, but prohibits human reproductive cloning.[54]
* 16 February, 2007 – The California Institute for Regenerative Medicine became the biggest financial backer of human embryonic stem cell research in the United States when they awarded nearly $45 million in research grants.[55]
* 04 November, 2008 - The people of the U.S. state of Michigan passed Proposal 08-2, allowing Michigan researchers to make embryonic stem cell cultures from excess embryos donated from fertility treatments.[56]
* 23 January, 2009 - Under the new President Barack Obama, the restrictions placed on federal funding of Stem Cell research in the United States were lifted.[57]
References
1. ^ Becker AJ, McCulloch EA, Till JE (1963). "Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells". Nature 197: 452–4. doi:10.1038/197452a0. PMID 13970094.
2. ^ Siminovitch L, McCulloch EA, Till JE (1963). "The distribution of colony-forming cells among spleen colonies". Journal of Cellular and Comparative Physiology 62: 327–36. doi:10.1002/jcp.1030620313. PMID 14086156.
3. ^ Tuch BE (2006). "Stem cells—a clinical update". Australian Family Physician 35 (9): 719–21. PMID 16969445.
4. ^ a b c d e f Hans R. Schöler (2007). "The Potential of Stem Cells: An Inventory". in Nikolaus Knoepffler, Dagmar Schipanski, and Stefan Lorenz Sorgner. Humanbiotechnology as Social Challenge. Ashgate Publishing, Ltd. pp. 28. ISBN 0754657558.
5. ^ Ulloa-Montoya F, Verfaillie CM, Hu WS (Jul 2005). "Culture systems for pluripotent stem cells". J Biosci Bioeng. 100 (1): 12–27. doi:10.1263/jbb.100.12. PMID 16233846.
6. ^ Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luria EA, Ruadkow IA (1974). "Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method". Exp Hematol 2 (2): 83–92. PMID 4455512.
7. ^ Friedenstein AJ, Gorskaja JF, Kulagina NN (1976). "Fibroblast precursors in normal and irradiated mouse hematopoietic organs". Exp Hematol 4 (5): 267–74. PMID 976387.
8. ^ FOXNews.com - New Stem-Cell Procedure Doesn't Harm Embryos, Company Claims - Biology | Astronomy | Chemistry | Physics
9. ^ Mouse Embryonic Stem (ES) Cell Culture-Current Protocols in Molecular Biology
10. ^ Culture of Human Embryonic Stem Cells (hESC) NIH
11. ^ Chambers I, Colby D, Robertson M, et al (2003). "Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells". Cell 113 (5): 643–55. doi:10.1016/S0092-8674(03)00392-1. PMID 12787505.
12. ^ Boyer LA, Lee TI, Cole MF, et al (2005). "Core transcriptional regulatory circuitry in human embryonic stem cells". Cell 122 (6): 947–56. doi:10.1016/j.cell.2005.08.020. PMID 16153702.
13. ^ Adewumi O, Aflatoonian B, Ahrlund-Richter L, et al (2007). "Characterization of human embryonic stem cell lines by the International Stem Cell Initiative". Nat. Biotechnol. 25 (7): 803–16. doi:10.1038/nbt1318. PMID 17572666.
14. ^ 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. PMID 9804556.
15. ^ Wu DC, Boyd AS, Wood KJ (2007). "Embryonic stem cell transplantation: potential applicability in cell replacement therapy and regenerative medicine". Front. Biosci. 12: 4525–35. doi:10.2741/2407. PMID 17485394.
16. ^ Jiang Y, Jahagirdar BN, Reinhardt RL, et al (2002). "Pluripotency of mesenchymal stem cells derived from adult marrow". Nature 418 (6893): 41–9. doi:10.1038/nature00870. PMID 12077603.
17. ^ Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M (2007). "A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues". Leukemia 21 (5): 860–7. doi:10.1038/sj.leu.2404630. PMID 17344915.
18. ^ Gardner RL (2002). "Stem cells: potency, plasticity and public perception". Journal of Anatomy 200 (3): 277–82. doi:10.1046/j.1469-7580.2002.00029.x. PMID 12033732.
19. ^ Takahashi K, Yamanaka S (2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors". Cell 126 (4): 663–76. doi:10.1016/j.cell.2006.07.024. PMID 16904174.
20. ^ Barrilleaux B, Phinney DG, Prockop DJ, O'Connor KC (2006). "Review: ex vivo engineering of living tissues with adult stem cells". Tissue Eng. 12 (11): 3007–19. doi:10.1089/ten.2006.12.3007. PMID 17518617.
21. ^ Gimble JM, Katz AJ, Bunnell BA (2007). "Adipose-derived stem cells for regenerative medicine". Circ. Res. 100 (9): 1249–60. doi:10.1161/01.RES.0000265074.83288.09. PMID 17495232.
22. ^ Bone Marrow Transplant
23. ^ Kane, Ed (2008-05-01). "Stem-cell therapy shows promise for horse soft-tissue injury, disease". DVM Newsmagazine. http://www.dvmnews.com/dvm/Equine+Medicine/Stem-cell-therapy-shows-promise-for-horse-soft-tis/ArticleStandard/Article/detail/515503. Retrieved on 2008-06-12.
24. ^ USDHHS Stem Cell FAQ 2004
25. ^ Beckmann J, Scheitza S, Wernet P, Fischer JC, Giebel B (2007). "Asymmetric cell division within the human hematopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins". Blood 109 (12): 5494–501. doi:10.1182/blood-2006-11-055921. PMID 17332245.
26. ^ Xie T, Spradling A (1998). "decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary". Cell 94 (2): 251–60. doi:10.1016/S0092-8674(00)81424-5. PMID 9695953.
27. ^ Song X, Zhu C, Doan C, Xie T (2002). "Germline stem cells anchored by adherens junctions in the Drosophila ovary niches". Science 296 (5574): 1855–7. doi:10.1126/science.1069871. PMID 12052957.
28. ^ Takahashi K, Yamanaka S (2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors". Cell 126 (4): 663–76. doi:10.1016/j.cell.2006.07.024. PMID 16904174.
29. ^ Gahrton G, Björkstrand B (2000). "Progress in haematopoietic stem cell transplantation for multiple myeloma". J Intern Med 248 (3): 185–201. doi:10.1046/j.1365-2796.2000.00706.x. PMID 10971785.
30. ^ Lindvall O (2003). "Stem cells for cell therapy in Parkinson's disease". Pharmacol Res 47 (4): 279–87. doi:10.1016/S1043-6618(03)00037-9. PMID 12644384.
31. ^ Goldman S, Windrem M (2006). "Cell replacement therapy in neurological disease". Philos Trans R Soc Lond B Biol Sci 361 (1473): 1463–75. doi:10.1098/rstb.2006.1886. PMID 16939969.
32. ^ Wade N (2006-08-14). "Some Scientists See Shift in Stem Cell Hopes". New York Times. http://www.nytimes.com/2006/08/14/washington/14stem.html. Retrieved on 2006-12-28.
33. ^ Firm Creates Stem Cells Without Hurting Embryos : NPR
34. ^ Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (November 1998). "Embryonic stem cell lines derived from human blastocysts". Science (New York, N.Y.) 282 (5391): 1145–7. doi:10.1126/science.282.5391.1145. PMID 9804556.
35. ^ Cibelli JB, Lanza RP, West MD, Ezzell C (Nov 2001). "The First Human Cloned Embryo". Scientific American. http://www.sciam.com/article.cfm?id=the-first-human-cloned-em.
36. ^ Shostak S (2006). "(Re)defining stem cells". Bioessays 28 (3): 301–8. doi:10.1002/bies.20376. PMID 16479584.
37. ^ Good News for Alcoholics | Biotechnology | DISCOVER Magazine
38. ^ Scotsman.com News
39. ^ De Coppi P, Bartsch G, Siddiqui MM, et al (Jan 2007). "Isolation of amniotic stem cell lines with potential for therapy". Nat Biotechnol. 25 (1): 100–6. doi:10.1038/nbt1274. PMID 17206138. http://www.nature.com/nbt/journal/v25/n1/abs/nbt1274.html.
40. ^ Amniotic fluid yields stem cells, Harvard researchers report - Boston.com
41. ^ Cyranoski D (2007). "Simple switch turns cells embryonic". Nature 447 (7145): 618–9. doi:10.1038/447618a. PMID 17554270.
42. ^ Mitalipov SM, Zhou Q, Byrne JA, Ji WZ, Norgren RB, Wolf DP (2007). "Reprogramming following somatic cell nuclear transfer in primates is dependent upon nuclear remodeling". Hum Reprod 22 (8): 2232–42. doi:10.1093/humrep/dem136. PMID 17562675.
43. ^ "The Nobel Prize in Physiology or Medicine 2007". Nobelprize.org. http://nobelprize.org/nobel_prizes/medicine/laureates/2007/index.html. Retrieved on 8 October 2007.
44. ^ Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (Nov 2007). "Induction of pluripotent stem cells from adult human fibroblasts by defined factors". Cell 131 (5): 861–72. doi:10.1016/j.cell.2007.11.019. PMID 18035408. http://images.cell.com/images/Edimages/Cell/IEPs/3661.pdf.
45. ^ Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (Dec 2007). "Induced pluripotent stem cell lines derived from human somatic cells". Science (journal) 318 (5858): 1917–20. doi:10.1126/science.1151526. PMID 18029452. http://www.sciencemag.org/cgi/content/abstract/1151526.
46. ^ Cell Stem Cell - Chung et al
47. ^ http://stemcells.alphamedpress.org/cgi/reprint/2007-0252v1.pdf
48. ^ Aoi T, Yae K, Nakagawa M, et al (Aug 2008). "Generation of pluripotent stem cells from adult mouse liver and stomach cells". Science 321 (5889): 699–702. doi:10.1126/science.1154884. PMID 18276851.
49. ^ The Niche: Adult cell types besides skin are reprogrammed
50. ^ Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D (2008). "Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells". Pain Physician 11 (3): 343–53. PMID 18523506. http://www.painphysicianjournal.com/linkout_vw.php?issn=1533-3159&vol=11&page=343.
51. ^ Conrad S, Renninger M, Hennenlotter J, et al (Nov 2008). "Generation of pluripotent stem cells from adult human testis". Nature 456 (7220): 344–9. doi:10.1038/nature07404. PMID 18849962.
52. ^ Baker M (Oct 2008). "Embryonic-like stem cells from a single human hair". Nature Reports Stem Cells. doi:10.1038/stemcells.2008.142. http://www.nature.com/stemcells/2008/0810/081030/full/stemcells.2008.142.html.
53. ^ a b Dispatches: The Politics of Stem Cells PBS
54. ^ Full-text of Missouri Constitution Amendment 2
55. ^ Calif. Awards $45M in Stem Cell Grants Associated Press, Feb. 17, 2007.
56. ^ Full-text of Michigan Proposal 08-2
57. ^ Green light for US stem cell work
External links
General
* Tell Me About Stem Cells: Quick and simple guide explaining the science behind stem cells
* Stem Cell Basics
* Nature Reports Stem Cells: Introductory material, research advances and debates concerning stem cell research.
* Understanding Stem Cells: A View of the Science and Issues from the National Academies
* Scientific American Magazine (June 2004 Issue) The Stem Cell Challenge
* Scientific American Magazine (July 2006 Issue) Stem Cells: The Real Culprits in Cancer?
* National Institutes of Health
* Stem Cell Research Forum of India
* Ethics of Stem Cell Research entry in the Stanford Encyclopedia of Philosophy by Andrew Siegel
* Isolation of amniotic stem cell lines with potential for therapy
Peer-reviewed journals
* STEM CELLS
* Cytotherapy
* Cloning and Stem Cells
* Stem Cells and Development
* Regenerative Medicine
* Stem Cell Research
They are characterized by the ability to renew themselves through mitotic cell division and differentiating into a diverse range of specialized cell types.
Research in the stem cell field grew out of findings by Canadian scientists Ernest A. McCulloch and James E.
Till in the 1960s the two broad types of mammalian stem cells are: embryonic stem cells that are isolated from the inner cell mass of blastocysts, and adult stem cells that are found in adult tissues.
In a developing embryo, stem cells can differentiate into all of the specialized embryonic tissues.
In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of regenerative organs, such as blood, skin or intestinal tissues.
Stem cells can now be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture.
Highly plastic adult stem cells from a variety of sources, including umbilical cord blood and bone marrow, are routinely used in medical therapies. Embryonic cell lines and autologous embryonic stem cells generated through therapeutic cloning have also been proposed as promising candidates for future therapies.
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.Properties
[plz click on the image to zoom it]
The classical definition of a stem cell requires that it possess two properties:
* Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
* Potency - the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent - to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells.
Potency definitions
Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[4]
* Totipotent (a.k.a omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable, organism.[4] These cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.[citation needed]
* Pluripotent stem cells are the descendants of totipotent cells and can differentiate into nearly all cells,[4] i.e. cells derived from any of the three germ layers.[5]
* Multipotent stem cells can differentiate into a number of cells, but only those of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).[4]
* Oligopotent stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem cells.[4]
* Unipotent cells can produce only one cell type, their own,[4] but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells).
Identification
The practical definition of a stem cell is the functional definition - the ability to regenerate tissue over a lifetime. For example, the gold standard test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.
Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, where single cells are characterized by their ability to differentiate and self-renew.[6][7] As well, stem cells can be isolated based on a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells.
Embryonic
Main article: Embryonic stem cell
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos.[8] A blastocyst is an early stage embryo—approximately four to five days old in humans and consisting of 50–150 cells. ES cells are pluripotent and give rise during development to 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. They do not contribute to the extra-embryonic membranes or the placenta.
Nearly all research to date has taken place using mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia Inhibitory Factor (LIF).[9] Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic Fibroblast Growth Factor (bFGF or FGF-2).[10] Without optimal culture conditions or genetic manipulation,[11] embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the presence of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and SOX2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[12] The cell surface antigens most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[13]
After nearly ten years of research[14], there are no approved treatments or human trials using embryonic stem cells. ES cells, being pluripotent cells, require specific signals for correct differentiation - if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[15] Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.
Adult
Main article: Adult stem cell
Stem cell division and differentiation. A - stem cell; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation
[plz click on the image to see it completely and to zoom it]
The term adult stem cell refers to any cell which is found in a developed organism that has two properties: the ability to divide and create another cell like itself and also divide and create a cell more differentiated than itself. Also known as somatic (from Greek Σωματικóς, "of the body") stem cells and germline (giving rise to gametes) stem cells, they can be found in children, as well as adults.[16]
Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood.[17] A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.[18] In mice, pluripotent stem cells are directly generated from adult fibroblast cultures. Unfortunately, many mice don't live long with stem cell organs [19]
Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, etc.).[20][21]
Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants.[22] Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.[23] The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, because in some instances adult stem cells can be obtained from the intended recipient, (an autograft) the risk of rejection is essentially non-existent in these situations. Consequently, more US government funding is being provided for adult stem cell research.[24]
Lineage
Main article: Stem cell line
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[25]
An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals dpp and adherens junctions that prevent germarium stem cells from differentiating.[26][27]
Main article: Induced Pluripotent Stem Cell
The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include several transcription factors including the oncogene c-Myc. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent.[28] However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy.
Treatments
Main article: Stem cell treatments
Medical researchers believe that stem cell therapy has the potential to dramatically change the treatment of human disease. A number of adult stem cell therapies already exist, particularly bone marrow transplants that are used to treat leukemia.[29] In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety of diseases including cancer, Parkinson's disease, spinal cord injuries, Amyotrophic lateral sclerosis, multiple sclerosis, and muscle damage, amongst a number of other impairments and conditions.[30][31] However, there still exists a great deal of social and scientific uncertainty surrounding stem cell research, which could possibly be overcome through public debate and future research, and further education of the public.
Stem cells, however, are already used extensively in research, and some scientists do not see cell therapy as the first goal of the research, but see the investigation of stem cells as a goal worthy in itself.[32]
Controversy surrounding research
Main article: Stem cell controversy
There exists a widespread controversy over human embryonic stem cell research that emanates from the techniques used in the creation and usage of stem cells. Human embryonic stem cell research is controversial because, with the present state of technology, starting a stem cell line requires the destruction of a human embryo and/or therapeutic cloning. However, recently, it has been shown in principle that adult stem cell lines can be manipulated to generate embryonic-like stem cell lines using a single-cell biopsy similar to that used in preimplantation genetic diagnosis that may allow stem cell creation without embryonic destruction.[33] It is not the entire field of stem cell research, but the specific field of human embryonic stem cell research that is at the centre of an ethical debate.
Opponents of the research argue that embryonic stem cell technologies are a slippery slope to reproductive cloning and can fundamentally devalue human life. Those in the pro-life movement argue that a human embryo is a human life and is therefore entitled to protection.
Contrarily, supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It is also noted that excess embryos created for in vitro fertilization could be donated with consent and used for the research.
The ensuing debate has prompted authorities around the world to seek regulatory frameworks and highlighted the fact that stem cell research represents a social and ethical challenge.
Key research events
* 1908 - The term "stem cell" was proposed for scientific use by the Russian histologist Alexander Maksimov (1874–1928) at congress of hematologic society in Berlin. It postulated existence of haematopoietic stem cells.
* 1960s - Joseph Altman and Gopal Das present scientific evidence of adult neurogenesis, ongoing stem cell activity in the brain; their reports contradict Cajal's "no new neurons" dogma and are largely ignored.
* 1963 - McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow.
* 1968 - Bone marrow transplant between two siblings successfully treats SCID.
* 1978 - Haematopoietic stem cells are discovered in human cord blood.
* 1981 - Mouse embryonic stem cells are derived from the inner cell mass by scientists Martin Evans, Matthew Kaufman, and Gail R. Martin. Gail Martin is attributed for coining the term "Embryonic Stem Cell".
* 1992 - Neural stem cells are cultured in vitro as neurospheres.
* 1997 - Leukemia is shown to originate from a haematopoietic stem cell, the first direct evidence for cancer stem cells.
* 1998 - James Thomson and coworkers derive the first human embryonic stem cell line at the University of Wisconsin-Madison.[34]
* 2000s - Several reports of adult stem cell plasticity are published.
* 2001 - Scientists at Advanced Cell Technology clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.[35]
* 2003 - Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth.[36]
* 2004–2005 - Korean researcher Hwang Woo-Suk claims to have created several human embryonic stem cell lines from unfertilised human oocytes. The lines were later shown to be fabricated.
* 2005 - Researchers at Kingston University in England claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical cord blood. The group claims these cells are able to differentiate into more types of tissue than adult stem cells.
* August 2006 - Rat Induced pluripotent stem cells: the journal Cell publishes Kazutoshi Takahashi and Shinya Yamanaka.
Takahashi K, Yamanaka S (Aug 2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors". Cell 126 (4): 663–76. doi:10.1016/j.cell.2006.07.024. PMID 16904174. http://www.cell.com/content/article/fulltext?uid=PIIS0092867406009767.
* October 2006 - Scientists at Newcastle University in England create the first ever artificial liver cells using umbilical cord blood stem cells.[37][38]
* January 2007 - Scientists at Wake Forest University led by Dr. Anthony Atala and Harvard University report discovery of a new type of stem cell in amniotic fluid.[39] This may potentially provide an alternative to embryonic stem cells for use in research and therapy.[40]
* June 2007 - Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.[41] In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer[42]
* October 2007 - Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.[43]
* November 2007 - Human Induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka, "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors",[44] and in Science by Junying Yu, et al., from the research group of James Thomson, "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells":[45] pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of tumorigenesis due to c-myc and retroviral gene transfer remains to be determined.
* January 2008 - Robert Lanza and colleagues at Advanced Cell Technology and UCSF create the first human embryonic stem cells without destruction of the embryo[46]
* January 2008 - Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts[47]
* February 2008 - Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach: these iPS cells seem to be more similar to embryonic stem cells than the previous developed iPS cells and not tumorigenic, moreover genes that are required for iPS cells do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques. [48][49]
* March 2008-The first published study of successful cartilage regeneration in the human knee using autologous adult mesenchymal stem cells is published by Clinicians from Regenerative Sciences[50]
* October 2008 - Sabine Conrad and colleagues at Tübingen, Germany generate pluripotent stem cells from spermatogonial cells of adult human testis by culturing the cells in vitro under leukemia inhibitory factor (LIF) supplementation. [51]
* 30 October 2008 - Embryonic-like stem cells from a single human hair.[52]
Funding & policy debate in the US
* 1993 - As per the National Institutes of Health Revitalization Act, Congress and President Bill Clinton give the NIH direct authority to fund human embryo research for the first time.[53]
* 1995 - The U.S. Congress passes an appropriations bill attached to which is a rider, the Dickey Amendment which prohibited federally appropriated funds to be used for research where human embryos would be either created or destroyed. President Clinton signs the bill into law. This predates the creation of the first human embryonic stem cell lines.
* 1999 - After the creation of the first human embryonic stem cell lines in 1998 by James Thomson of the University of Wisconsin, Harriet Rabb, the top lawyer at the Department of Health and Human Services, releases a legal opinion that would set the course for Clinton Administration policy. Federal funds, obviously, could not be used to derive stem cell lines (because derivation involves embryo destruction). However, she concludes that because human embryonic stem cells "are not a human embryo within the statutory definition," the Dickey-Wicker Amendment does not apply to them. The NIH was therefore free to give federal funding to experiments involving the cells themselves. President Clinton strongly endorses the new guidelines, noting that human embryonic stem cell research promised "potentially staggering benefits." And with the guidelines in place, the NIH begins accepting grant proposals from scientists.[53]
* 02 November, 2004 - California voters approve Proposition 71, which provides $3 billion in state funds over ten years to human embryonic stem cell research.
* 2001–2006 - U.S. President George W. Bush signs an executive order which restricts federally-funded stem cell research on embryonic stem cells to the already derived cell lines. He supports federal funding for embryonic stem cell research on the already existing lines of approximately $100 million and $250 million for research on adult and animal stem cells.
* 5 May, 2006 - Senator Rick Santorum introduces bill number S. 2754, or the Alternative Pluripotent Stem Cell Therapies Enhancement Act, into the U.S. Senate.
* 18 July, 2006 - The U.S. Senate passes the Stem Cell Research Enhancement Act H.R. 810 and votes down Senator Santorum's S. 2754.
* 19 July, 2006 - President George W. Bush vetoes H.R. 810 (Stem Cell Research Enhancement Act), a bill that would have reversed the Dickey Amendment which made it illegal for federal money to be used for research where stem cells are derived from the destruction of an embryo.
* 07 November, 2006 - The people of the U.S. state of Missouri passed Amendment 2, which allows usage of any stem cell research and therapy allowed under federal law, but prohibits human reproductive cloning.[54]
* 16 February, 2007 – The California Institute for Regenerative Medicine became the biggest financial backer of human embryonic stem cell research in the United States when they awarded nearly $45 million in research grants.[55]
* 04 November, 2008 - The people of the U.S. state of Michigan passed Proposal 08-2, allowing Michigan researchers to make embryonic stem cell cultures from excess embryos donated from fertility treatments.[56]
* 23 January, 2009 - Under the new President Barack Obama, the restrictions placed on federal funding of Stem Cell research in the United States were lifted.[57]
References
1. ^ Becker AJ, McCulloch EA, Till JE (1963). "Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells". Nature 197: 452–4. doi:10.1038/197452a0. PMID 13970094.
2. ^ Siminovitch L, McCulloch EA, Till JE (1963). "The distribution of colony-forming cells among spleen colonies". Journal of Cellular and Comparative Physiology 62: 327–36. doi:10.1002/jcp.1030620313. PMID 14086156.
3. ^ Tuch BE (2006). "Stem cells—a clinical update". Australian Family Physician 35 (9): 719–21. PMID 16969445.
4. ^ a b c d e f Hans R. Schöler (2007). "The Potential of Stem Cells: An Inventory". in Nikolaus Knoepffler, Dagmar Schipanski, and Stefan Lorenz Sorgner. Humanbiotechnology as Social Challenge. Ashgate Publishing, Ltd. pp. 28. ISBN 0754657558.
5. ^ Ulloa-Montoya F, Verfaillie CM, Hu WS (Jul 2005). "Culture systems for pluripotent stem cells". J Biosci Bioeng. 100 (1): 12–27. doi:10.1263/jbb.100.12. PMID 16233846.
6. ^ Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luria EA, Ruadkow IA (1974). "Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method". Exp Hematol 2 (2): 83–92. PMID 4455512.
7. ^ Friedenstein AJ, Gorskaja JF, Kulagina NN (1976). "Fibroblast precursors in normal and irradiated mouse hematopoietic organs". Exp Hematol 4 (5): 267–74. PMID 976387.
8. ^ FOXNews.com - New Stem-Cell Procedure Doesn't Harm Embryos, Company Claims - Biology | Astronomy | Chemistry | Physics
9. ^ Mouse Embryonic Stem (ES) Cell Culture-Current Protocols in Molecular Biology
10. ^ Culture of Human Embryonic Stem Cells (hESC) NIH
11. ^ Chambers I, Colby D, Robertson M, et al (2003). "Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells". Cell 113 (5): 643–55. doi:10.1016/S0092-8674(03)00392-1. PMID 12787505.
12. ^ Boyer LA, Lee TI, Cole MF, et al (2005). "Core transcriptional regulatory circuitry in human embryonic stem cells". Cell 122 (6): 947–56. doi:10.1016/j.cell.2005.08.020. PMID 16153702.
13. ^ Adewumi O, Aflatoonian B, Ahrlund-Richter L, et al (2007). "Characterization of human embryonic stem cell lines by the International Stem Cell Initiative". Nat. Biotechnol. 25 (7): 803–16. doi:10.1038/nbt1318. PMID 17572666.
14. ^ 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. PMID 9804556.
15. ^ Wu DC, Boyd AS, Wood KJ (2007). "Embryonic stem cell transplantation: potential applicability in cell replacement therapy and regenerative medicine". Front. Biosci. 12: 4525–35. doi:10.2741/2407. PMID 17485394.
16. ^ Jiang Y, Jahagirdar BN, Reinhardt RL, et al (2002). "Pluripotency of mesenchymal stem cells derived from adult marrow". Nature 418 (6893): 41–9. doi:10.1038/nature00870. PMID 12077603.
17. ^ Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M (2007). "A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues". Leukemia 21 (5): 860–7. doi:10.1038/sj.leu.2404630. PMID 17344915.
18. ^ Gardner RL (2002). "Stem cells: potency, plasticity and public perception". Journal of Anatomy 200 (3): 277–82. doi:10.1046/j.1469-7580.2002.00029.x. PMID 12033732.
19. ^ Takahashi K, Yamanaka S (2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors". Cell 126 (4): 663–76. doi:10.1016/j.cell.2006.07.024. PMID 16904174.
20. ^ Barrilleaux B, Phinney DG, Prockop DJ, O'Connor KC (2006). "Review: ex vivo engineering of living tissues with adult stem cells". Tissue Eng. 12 (11): 3007–19. doi:10.1089/ten.2006.12.3007. PMID 17518617.
21. ^ Gimble JM, Katz AJ, Bunnell BA (2007). "Adipose-derived stem cells for regenerative medicine". Circ. Res. 100 (9): 1249–60. doi:10.1161/01.RES.0000265074.83288.09. PMID 17495232.
22. ^ Bone Marrow Transplant
23. ^ Kane, Ed (2008-05-01). "Stem-cell therapy shows promise for horse soft-tissue injury, disease". DVM Newsmagazine. http://www.dvmnews.com/dvm/Equine+Medicine/Stem-cell-therapy-shows-promise-for-horse-soft-tis/ArticleStandard/Article/detail/515503. Retrieved on 2008-06-12.
24. ^ USDHHS Stem Cell FAQ 2004
25. ^ Beckmann J, Scheitza S, Wernet P, Fischer JC, Giebel B (2007). "Asymmetric cell division within the human hematopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins". Blood 109 (12): 5494–501. doi:10.1182/blood-2006-11-055921. PMID 17332245.
26. ^ Xie T, Spradling A (1998). "decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary". Cell 94 (2): 251–60. doi:10.1016/S0092-8674(00)81424-5. PMID 9695953.
27. ^ Song X, Zhu C, Doan C, Xie T (2002). "Germline stem cells anchored by adherens junctions in the Drosophila ovary niches". Science 296 (5574): 1855–7. doi:10.1126/science.1069871. PMID 12052957.
28. ^ Takahashi K, Yamanaka S (2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors". Cell 126 (4): 663–76. doi:10.1016/j.cell.2006.07.024. PMID 16904174.
29. ^ Gahrton G, Björkstrand B (2000). "Progress in haematopoietic stem cell transplantation for multiple myeloma". J Intern Med 248 (3): 185–201. doi:10.1046/j.1365-2796.2000.00706.x. PMID 10971785.
30. ^ Lindvall O (2003). "Stem cells for cell therapy in Parkinson's disease". Pharmacol Res 47 (4): 279–87. doi:10.1016/S1043-6618(03)00037-9. PMID 12644384.
31. ^ Goldman S, Windrem M (2006). "Cell replacement therapy in neurological disease". Philos Trans R Soc Lond B Biol Sci 361 (1473): 1463–75. doi:10.1098/rstb.2006.1886. PMID 16939969.
32. ^ Wade N (2006-08-14). "Some Scientists See Shift in Stem Cell Hopes". New York Times. http://www.nytimes.com/2006/08/14/washington/14stem.html. Retrieved on 2006-12-28.
33. ^ Firm Creates Stem Cells Without Hurting Embryos : NPR
34. ^ Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (November 1998). "Embryonic stem cell lines derived from human blastocysts". Science (New York, N.Y.) 282 (5391): 1145–7. doi:10.1126/science.282.5391.1145. PMID 9804556.
35. ^ Cibelli JB, Lanza RP, West MD, Ezzell C (Nov 2001). "The First Human Cloned Embryo". Scientific American. http://www.sciam.com/article.cfm?id=the-first-human-cloned-em.
36. ^ Shostak S (2006). "(Re)defining stem cells". Bioessays 28 (3): 301–8. doi:10.1002/bies.20376. PMID 16479584.
37. ^ Good News for Alcoholics | Biotechnology | DISCOVER Magazine
38. ^ Scotsman.com News
39. ^ De Coppi P, Bartsch G, Siddiqui MM, et al (Jan 2007). "Isolation of amniotic stem cell lines with potential for therapy". Nat Biotechnol. 25 (1): 100–6. doi:10.1038/nbt1274. PMID 17206138. http://www.nature.com/nbt/journal/v25/n1/abs/nbt1274.html.
40. ^ Amniotic fluid yields stem cells, Harvard researchers report - Boston.com
41. ^ Cyranoski D (2007). "Simple switch turns cells embryonic". Nature 447 (7145): 618–9. doi:10.1038/447618a. PMID 17554270.
42. ^ Mitalipov SM, Zhou Q, Byrne JA, Ji WZ, Norgren RB, Wolf DP (2007). "Reprogramming following somatic cell nuclear transfer in primates is dependent upon nuclear remodeling". Hum Reprod 22 (8): 2232–42. doi:10.1093/humrep/dem136. PMID 17562675.
43. ^ "The Nobel Prize in Physiology or Medicine 2007". Nobelprize.org. http://nobelprize.org/nobel_prizes/medicine/laureates/2007/index.html. Retrieved on 8 October 2007.
44. ^ Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (Nov 2007). "Induction of pluripotent stem cells from adult human fibroblasts by defined factors". Cell 131 (5): 861–72. doi:10.1016/j.cell.2007.11.019. PMID 18035408. http://images.cell.com/images/Edimages/Cell/IEPs/3661.pdf.
45. ^ Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (Dec 2007). "Induced pluripotent stem cell lines derived from human somatic cells". Science (journal) 318 (5858): 1917–20. doi:10.1126/science.1151526. PMID 18029452. http://www.sciencemag.org/cgi/content/abstract/1151526.
46. ^ Cell Stem Cell - Chung et al
47. ^ http://stemcells.alphamedpress.org/cgi/reprint/2007-0252v1.pdf
48. ^ Aoi T, Yae K, Nakagawa M, et al (Aug 2008). "Generation of pluripotent stem cells from adult mouse liver and stomach cells". Science 321 (5889): 699–702. doi:10.1126/science.1154884. PMID 18276851.
49. ^ The Niche: Adult cell types besides skin are reprogrammed
50. ^ Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D (2008). "Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells". Pain Physician 11 (3): 343–53. PMID 18523506. http://www.painphysicianjournal.com/linkout_vw.php?issn=1533-3159&vol=11&page=343.
51. ^ Conrad S, Renninger M, Hennenlotter J, et al (Nov 2008). "Generation of pluripotent stem cells from adult human testis". Nature 456 (7220): 344–9. doi:10.1038/nature07404. PMID 18849962.
52. ^ Baker M (Oct 2008). "Embryonic-like stem cells from a single human hair". Nature Reports Stem Cells. doi:10.1038/stemcells.2008.142. http://www.nature.com/stemcells/2008/0810/081030/full/stemcells.2008.142.html.
53. ^ a b Dispatches: The Politics of Stem Cells PBS
54. ^ Full-text of Missouri Constitution Amendment 2
55. ^ Calif. Awards $45M in Stem Cell Grants Associated Press, Feb. 17, 2007.
56. ^ Full-text of Michigan Proposal 08-2
57. ^ Green light for US stem cell work
External links
General
* Tell Me About Stem Cells: Quick and simple guide explaining the science behind stem cells
* Stem Cell Basics
* Nature Reports Stem Cells: Introductory material, research advances and debates concerning stem cell research.
* Understanding Stem Cells: A View of the Science and Issues from the National Academies
* Scientific American Magazine (June 2004 Issue) The Stem Cell Challenge
* Scientific American Magazine (July 2006 Issue) Stem Cells: The Real Culprits in Cancer?
* National Institutes of Health
* Stem Cell Research Forum of India
* Ethics of Stem Cell Research entry in the Stanford Encyclopedia of Philosophy by Andrew Siegel
* Isolation of amniotic stem cell lines with potential for therapy
Peer-reviewed journals
* STEM CELLS
* Cytotherapy
* Cloning and Stem Cells
* Stem Cells and Development
* Regenerative Medicine
* Stem Cell Research
STEM CELL BANK SOURCE--DECIDUOUS (MILK) TEETH & WISDOM TEETH
[plz click on the image to zoom it]
WORLD'S 1ST BABY TOOTH STEM CELL BANK
BioEden (registered with the FDA), is the first fully operational processing laboratory and storage bank for primary teeth stem cells to open in the U.S. Their state-of-the-art facilities are located in Austin, Texas, and will serve children and their families nationwide. BioEden is also the only cell storage facility willing to guarantee their services.
The stem cells found in children’s primary teeth are a viable, ethical, and morally non-controversial alternative to the possibilities offered by embryonic stem cells. BioEden, Inc. was founded to bring this exciting technology to the American public at an affordable price.
According to President Jeff Johnson, the process is simple, when your child’s tooth begins to loosen, call them. They will send you a kit with processing instructions, and make arrangements to have the tooth transported to their facility in Austin, Texas where the cells contained in the tooth will be removed and stored in a special process that keeps them viable for the future. It is critical that the cells be extracted quickly after the tooth falls out, and there are only 12 teeth that can be used for this process — not every tooth contains cells with this potential.
Dr. Songao Shi, Principle Investigator of the Dental Biology Unit at the National Institute of Health, identified adult stem cells in primary children’s teeth in 2003. Progenitor cells discovered include adiposites, osteoblasts, chondracytes, and mesenchymal stem cells. These types of cells are all being investigated for their ability to therapeutically treat many human diseases including heart disease, bone regeneration, and most promisingly neuronal degenerative disorders such as Alzheimer’s, Parkinson’s, and spinal cord injury.
In a major breakthrough in stem cell study researchers find human teeth can be a potential source of stem cell. Researchers are very sure about the source, so much that two US companies have offered special jar to preserve human teeth that are no more in use. Unfortunately, they find no users so far.
One such company is StemSave. The company charges a one-time fee of $590 and annual fees of $100 for storage.
Researchers have found that human exfoliated deciduous teeth had cells that showed positive results in tests with mice. So the exfoliated teeth may be an unexpected unique resource for stem-cell therapies including autologous stem-cell transplantation and tissue engineering.
However, others says that freezing teeth is no exception.It is similar to current practice of freezing sperm, eggs or embryos for future use, or maybe more like freezing the body or head of dead people in the hope that future technology will find a way to make it worth the trouble.
Source: Newsok
Someday, dentists might be able to repair cavities with stem cells instead of synthetic fillings. And on the "long-term horizon," dental stem cells might be used to regrow teeth for people who otherwise would need dentures, Stansbury said.
Tuesday, February 17, 2009
DIFFERENT WAYS OF STAGING CANCERS
There are different ways of staging cancers. The two main ways are the TNM system and number system.
TNM stages of mouth and oropharyngeal cancers
‘TNM’ stands for Tumour, Node and Metastasis. The system describes
* The size of a primary tumour (T)
* Whether the cancer has spread to the lymph nodes (N)
* Whether the cancer has spread to a different part of the body (M)
‘T’ stages of mouth cancer
There are 4 main 'T' stages of mouth and oropharyngeal cancer
* T1 means the tumour is contained within the tissue of the mouth or oropharynx and is no larger than 2cm (3/4 inch)
* T2 means the tumour is larger than 2cm, but smaller than 4cm (about 1 ½ inches)
* T3 means the tumour is bigger than 4cm
* T4 means the tumour has grown further than the mouth or oropharynx and into nearby body tissues such as bone, tissues of the neck, neck muscles, tongue, skin, sinuses or the voice box (larynx)
‘N’ stages of mouth cancer
There are 4 main lymph node stages in cancer of the mouth and oropharynx. One of these, stage N2, is broken down into 3 sub-stages. The important points here are whether there is cancer in any of the lymph nodes and if so, the size of the node and which side of the neck it is on.
* N0 means there are no cancer cells in the lymph nodes
* N1 means there are cancer cells in 1 lymph node on the same side of the neck as the cancer, but the node is less than 3cm across
* N2a means there is cancer in 1 lymph node on the same side of the neck, and the node is more than 3cm across but less than 6cm across
* N2b means there is cancer in more than 1 lymph node, but none of these nodes are more than 6cm across. All the affected nodes are on the same side of the neck as the cancer.
* N2c means there is cancer in nodes on the other side of the neck, or in nodes on both sides, but none of these nodes are more than 6cm across
* N3 means that at least 1 node containing cancer is more than 6cm across
‘M’ stages of mouth cancer
There are two stages to describe spread of cancer of the mouth and oropharynx to other parts of the body
* M0 means there is no cancer spread to other parts of the body
* M1 means the cancer has spread to other parts of the body, such as the lungs
Together, the T, N and M stages give a complete description of the stage of your cancer. For example, if you have a T2, N0, M0 cancer, you have a tumour larger than 2cm but not larger than 4cm. The lymph nodes are clear and there is no spread of your cancer to other parts of the body.
Number stages of mouth cancers
There are four main stages in this system – stages 1 to 4. Some doctors also refer to stage 0.
Stage 0 or carcinoma in situ (CIS)
If you have CIS or stage 0 cancer of the mouth, you have a very early stage cancer. Some doctors prefer to call this pre-cancer. There are cancer cells there. But they are all contained entirely within the lining of the mouth or oropharynx. So they have not spread. As the cells have not spread, this is not yet a true cancer. If the pre-cancer is not treated, there is a high chance of this condition going on to develop into an invasive cancer.
Stage 1
This is the earliest stage of invasive cancer. It means that cancer has begun to grow through the tissues lining the mouth and into the deeper tissues underneath. The cancer is no more than 2 cm across and has not spread to nearby tissues, lymph nodes or other organs.
Stage 2
If you have stage 2 mouth cancer, the tumour is larger than 2 cm across, but less than 4cm. The cancer has not spread to lymph nodes or any other organs.
Stage 3
Having stage 3 mouth cancer can mean one of two things. Either the cancer is bigger than 4cm but has not spread to any lymph nodes or other parts of the body. Or the tumour is any size but has spread to one lymph node on the same side of the neck as the cancer. In this case the lymph node involved is no more than 3cm across.
Stage 4
This means the cancer is advanced. Stage 4 can mean one of 3 things
* The cancer has grown through the tissues around the lips and mouth - lymph nodes in the area may or may not contain cancer cells
* The cancer is any size and has spread to more than 1 lymph node on the same side of the neck as the cancer, or to lymph nodes on both sides of the neck, or to any lymph node that is bigger than 6cm
* The cancer has spread to other parts of the body such as the lungs or bones
The different grades of mouth and oropharyngeal cancer
The grade of a cancer tells you what the cells look like under a microscope. ` They are 'graded' according to how normal or abnormal they appear. There are 4 grades of oral and oropharyngeal cancer cells
* Grade 1 (low grade) – the cancer cells look very much like normal mouth or oropharyngeal
* Grade 2 (intermediate grade) – the cancer cells look slightly like normal mouth or oropharyngeal cells
* Grade 3 (high grade) – the cancer cells look very abnormal and not much like normal mouth or oropharyngeal cells
* Grade 4 (high grade) - the cancer cells do not look anything like normal mouth or oropharyngeal cells
Differentiation means how developed or mature a cell is. So you may hear your doctor describe grade 1 cancer cells as 'well differentiated'. Grade 2 cancer cells are 'moderately differentiated'. Grade 3 cancer cells are 'poorly differentiated'.
The grade of the cancer gives your specialist a 'rule of thumb' as to how the cancer is likely to behave. Low grade cancers are usually slower growing and less likely to spread. High grade cancers are likely to be faster growing and more likely to spread. This is only a guide. Your specialist will consider all your test results when deciding which treatment options are best for you.
TNM stages of mouth and oropharyngeal cancers
‘TNM’ stands for Tumour, Node and Metastasis. The system describes
* The size of a primary tumour (T)
* Whether the cancer has spread to the lymph nodes (N)
* Whether the cancer has spread to a different part of the body (M)
‘T’ stages of mouth cancer
There are 4 main 'T' stages of mouth and oropharyngeal cancer
* T1 means the tumour is contained within the tissue of the mouth or oropharynx and is no larger than 2cm (3/4 inch)
* T2 means the tumour is larger than 2cm, but smaller than 4cm (about 1 ½ inches)
* T3 means the tumour is bigger than 4cm
* T4 means the tumour has grown further than the mouth or oropharynx and into nearby body tissues such as bone, tissues of the neck, neck muscles, tongue, skin, sinuses or the voice box (larynx)
‘N’ stages of mouth cancer
There are 4 main lymph node stages in cancer of the mouth and oropharynx. One of these, stage N2, is broken down into 3 sub-stages. The important points here are whether there is cancer in any of the lymph nodes and if so, the size of the node and which side of the neck it is on.
* N0 means there are no cancer cells in the lymph nodes
* N1 means there are cancer cells in 1 lymph node on the same side of the neck as the cancer, but the node is less than 3cm across
* N2a means there is cancer in 1 lymph node on the same side of the neck, and the node is more than 3cm across but less than 6cm across
* N2b means there is cancer in more than 1 lymph node, but none of these nodes are more than 6cm across. All the affected nodes are on the same side of the neck as the cancer.
* N2c means there is cancer in nodes on the other side of the neck, or in nodes on both sides, but none of these nodes are more than 6cm across
* N3 means that at least 1 node containing cancer is more than 6cm across
‘M’ stages of mouth cancer
There are two stages to describe spread of cancer of the mouth and oropharynx to other parts of the body
* M0 means there is no cancer spread to other parts of the body
* M1 means the cancer has spread to other parts of the body, such as the lungs
Together, the T, N and M stages give a complete description of the stage of your cancer. For example, if you have a T2, N0, M0 cancer, you have a tumour larger than 2cm but not larger than 4cm. The lymph nodes are clear and there is no spread of your cancer to other parts of the body.
Number stages of mouth cancers
There are four main stages in this system – stages 1 to 4. Some doctors also refer to stage 0.
Stage 0 or carcinoma in situ (CIS)
If you have CIS or stage 0 cancer of the mouth, you have a very early stage cancer. Some doctors prefer to call this pre-cancer. There are cancer cells there. But they are all contained entirely within the lining of the mouth or oropharynx. So they have not spread. As the cells have not spread, this is not yet a true cancer. If the pre-cancer is not treated, there is a high chance of this condition going on to develop into an invasive cancer.
Stage 1
This is the earliest stage of invasive cancer. It means that cancer has begun to grow through the tissues lining the mouth and into the deeper tissues underneath. The cancer is no more than 2 cm across and has not spread to nearby tissues, lymph nodes or other organs.
Stage 2
If you have stage 2 mouth cancer, the tumour is larger than 2 cm across, but less than 4cm. The cancer has not spread to lymph nodes or any other organs.
Stage 3
Having stage 3 mouth cancer can mean one of two things. Either the cancer is bigger than 4cm but has not spread to any lymph nodes or other parts of the body. Or the tumour is any size but has spread to one lymph node on the same side of the neck as the cancer. In this case the lymph node involved is no more than 3cm across.
Stage 4
This means the cancer is advanced. Stage 4 can mean one of 3 things
* The cancer has grown through the tissues around the lips and mouth - lymph nodes in the area may or may not contain cancer cells
* The cancer is any size and has spread to more than 1 lymph node on the same side of the neck as the cancer, or to lymph nodes on both sides of the neck, or to any lymph node that is bigger than 6cm
* The cancer has spread to other parts of the body such as the lungs or bones
The different grades of mouth and oropharyngeal cancer
The grade of a cancer tells you what the cells look like under a microscope. ` They are 'graded' according to how normal or abnormal they appear. There are 4 grades of oral and oropharyngeal cancer cells
* Grade 1 (low grade) – the cancer cells look very much like normal mouth or oropharyngeal
* Grade 2 (intermediate grade) – the cancer cells look slightly like normal mouth or oropharyngeal cells
* Grade 3 (high grade) – the cancer cells look very abnormal and not much like normal mouth or oropharyngeal cells
* Grade 4 (high grade) - the cancer cells do not look anything like normal mouth or oropharyngeal cells
Differentiation means how developed or mature a cell is. So you may hear your doctor describe grade 1 cancer cells as 'well differentiated'. Grade 2 cancer cells are 'moderately differentiated'. Grade 3 cancer cells are 'poorly differentiated'.
The grade of the cancer gives your specialist a 'rule of thumb' as to how the cancer is likely to behave. Low grade cancers are usually slower growing and less likely to spread. High grade cancers are likely to be faster growing and more likely to spread. This is only a guide. Your specialist will consider all your test results when deciding which treatment options are best for you.
EARLY IDENTIFICATION OF ABNORMAL SYMPTOMS IN MOUTH
It is important to have a self-awareness and to perform regular, self-examinations to help in the early identification of these symptoms:
1. A sore or ulcer in the mouth that does not heal within three weeks
2. A lump or overgrowth of tissue anywhere in the mouth
3. A white or red patch on the gums, tongue, or lining of the mouth
4. Difficulty in swallowing
5. Difficulty in chewing or moving the jaw or tongue
6. Numbness of the tongue or other area of the mouth
7. A feeling that something is caught in the throat
8. A chronic sore throat or hoarseness that persists more than six weeks, particularly smokers over 50 years old and heavy drinkers
9. Swelling of the jaw that causes dentures to fit poorly or become uncomfortable
10. Neck swelling present for more than three weeks
11. Unexplained tooth mobility persisting for more than three weeks - see a dentist urgently
12. Unilateral nasal mass / ulceration / obstruction, particularly associated with purulent or bloody discharge
1. A sore or ulcer in the mouth that does not heal within three weeks
2. A lump or overgrowth of tissue anywhere in the mouth
3. A white or red patch on the gums, tongue, or lining of the mouth
4. Difficulty in swallowing
5. Difficulty in chewing or moving the jaw or tongue
6. Numbness of the tongue or other area of the mouth
7. A feeling that something is caught in the throat
8. A chronic sore throat or hoarseness that persists more than six weeks, particularly smokers over 50 years old and heavy drinkers
9. Swelling of the jaw that causes dentures to fit poorly or become uncomfortable
10. Neck swelling present for more than three weeks
11. Unexplained tooth mobility persisting for more than three weeks - see a dentist urgently
12. Unilateral nasal mass / ulceration / obstruction, particularly associated with purulent or bloody discharge
Sunday, February 15, 2009
Crown down Pressureless Technique
Begin at the coronal portion with Gates-Gliddens
Continue down the canal, reducing the size of each file as you get closer to the apex
Your goal is to achieve a funnel shape
Description: In the crown down technique the dentist essentially works from the crown of the tooth, shaping the canal as he or she moves towards the apex. The instruments are used in a large to small sequence. The first instruments are the Gates-Gliddens which do the coronal flaring. The Peeso reamers or Hedstrom files follow in the mid-root region. Finally, progressively smaller files take the dentist towards the apex.
1. Insert #35 file until it just binds and measure depth - this is the “radicular access length”
2. Flare coronal portion of canal using #2 and #3 Gates to radicular access length
3. Starting with #30 file, insert beyond radicular access length until resistance first encountered
4. Rotate #30 clockwise two full rotations using NO pressure
5. Step down using sequentially smaller files rotated as in #4 above to a point 3mm from the radiographic apex. This is the “provisional working length”. Take a radiograph with the file at the provisional WL and estimate your “true” WL.
6. Continue stepping down with smaller files to the true WL
7. Place a #35 file until resistance is just met (should be at or beyond your radicular access length)
8. Rotate passively two full turns and then proceed with smaller files in step-down to the true WL
Continue down the canal, reducing the size of each file as you get closer to the apex
Your goal is to achieve a funnel shape
Description: In the crown down technique the dentist essentially works from the crown of the tooth, shaping the canal as he or she moves towards the apex. The instruments are used in a large to small sequence. The first instruments are the Gates-Gliddens which do the coronal flaring. The Peeso reamers or Hedstrom files follow in the mid-root region. Finally, progressively smaller files take the dentist towards the apex.
1. Insert #35 file until it just binds and measure depth - this is the “radicular access length”
2. Flare coronal portion of canal using #2 and #3 Gates to radicular access length
3. Starting with #30 file, insert beyond radicular access length until resistance first encountered
4. Rotate #30 clockwise two full rotations using NO pressure
5. Step down using sequentially smaller files rotated as in #4 above to a point 3mm from the radiographic apex. This is the “provisional working length”. Take a radiograph with the file at the provisional WL and estimate your “true” WL.
6. Continue stepping down with smaller files to the true WL
7. Place a #35 file until resistance is just met (should be at or beyond your radicular access length)
8. Rotate passively two full turns and then proceed with smaller files in step-down to the true WL
Coronal Flaring
The concept of Coronal Flaring came as a major breakthrough in endodontics. Instead of heading directly to the apical area, this approach cleaned up the coronal part, of thousands of micro organisms, thus preventing their entry to the apical part. But an unfortunate thing that has happened is that while so much stress is being given to the coronal enlargement, the apical area has been neglected.
Instrument Removal System
This system is a breakthrough endodontic device designed to mechanically engage and remove many intracanal obstructions.
EndoActivator System
The EndoActivator was developed by Drs. Pierre Machtou, Bob Sharp and Cliff Ruddle, and is designed to safely and vigorously energize the hydrodynamic phenomenon. Activated fluids promote deep cleaning and disinfection. Complete cleaning facilitates 3-D endodontics and long-term success.
Endodontic Microbrushes
Rotary tapered microbrushes may be used with various irrigants to optimally finish a root canal preparation following shaping procedures.
Tuesday, February 10, 2009
ProTaper®Universal Rotary Instruments
ProTaper® Universal SEM of
Active Cutting Surface
ProTaper® Universal nickel titanium rotary files are specially designed to instrument difficult, highly calcified, and severely curved root canals. The patented progressive taper, and advanced flute design provide the flexibility and efficiency to achieve consistent, successful cleaning and shaping when faced with these challenges
The finishing files, or F1, F2, F3, F4 and F5 instruments, have been designed to optimally finish the apical one-third, they do subtly and progressively expand the shape in the middle one-third of the canal. Generally, only one finishing instrument is required to prepare the apical one-third of a canal and the one selected is based on the canal's curvature and cross-sectional diameter.
The SX or Shaping X file is an accessory file and is used to optimally shape canals in shorter roots, relocate canals away from external root concavities, and to produce more shape, as desired, in the coronal aspects of canals in longer roots.
X GATE
Use this unique instrument to experience all the advantages of Gates 1-4 with maximal efficiency and simplicity. X-Gates features: • The tip of Gates 1 for easy insertion of the drill into the coronal third of the root canal. • The maximum diameter of Gates 4 for efficient relocation of the root canal opening. • The shaft of Gates 3 for improved strength. Use with a brushing action on the withdrawal stroke to intentionally relocate the canal away from the furcal danger. Also use to flatten, widen and finish the internal axial walls. In addition, its abrasively coated rounded tip enables you to precisely finish the pulpal floor.
ENDOACTIVATOR
The EndoActivator® System is designed to safely and vigorously energize the hydrodynamic phenomenon. Activated fluids promote deep cleaning and disinfection into lateral canals, fins, webs, and anastomoses. A cleaned root canal system facilitates 3-D obturation and long-term success. Activate your endodontic solutions today with this easy-to-use technology!
Sunday, February 8, 2009
Saturday, February 7, 2009
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