Stem cells
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Stem cells
- 2. Presenters: Ndjamen Herman, Nwanevu Sylvanus Akogu Enemona. DATE : 22 OF MARCH 2012
- 3. Contents Types of stem cells & sources. Aim of stem cell research Challenges faced by the research Material and Methods 4 1 2 3 Uses of stem cells5
- 4. What is a stem cell. stem cell SELF-RENEWAL (copying) specialized cell e.g. muscle cell, nerve cell DIFFERENTIATION (specializing) stem cell
- 5. Stem cell jargon. POTENCY MULTIPOTENT Can self renew for a long period of time and Can make multiple types of specialized cells ( adult stem cells PLURIPOTENT Able to differentiate into any of the three germ layers ( embryonic stem cells ). I-PLURIPOTENT artificially derived from a non-pluripotent cell by inducing a “forced “ expression of certain genes. TOTIPOTENT can differentiate into all types of specialized cells in the body including extra-embryonic tissues (zygote )
- 6. blastocyst outer layer of cells = ‘trophectoderm’ cells inside = ‘inner cell mass’ embryonic stem cells taken from the inner cell mass culture in the lab to grow more cells fluid with nutrients Embryonic stem cells Where they are found
- 7. Embryonic stem (ES) cells: What they can do all possible types of specialized cells differentiationembryonic stem cells PLURIPOTENT
- 8. Embryonic stem (ES) cells: Challenges blood skin liver neurons embryonic stem cells ?
- 9. Tissue stem cells: Where we find them surface of the eye skin testicles muscles brain breast intestines (gut) bone marrow
- 10. Induced pluripotent stem cells (iPS cells). cell from the body ‘genetic reprogramming’ = add certain genes to the cell induced pluripotent stem (iPS) cell behaves like an embryonic stem cell all possible types of specialized cells culture iPS cells in the lab differentiation Advantage: no need for embryos!
- 12. Tissue stem cells: Hematopoietic stem cells (HSCs) committed progenitors neutrophil NK cell erythrocytes dendritic cell platelet s megakaryocyte macrophage eosinophil basophil B cell T cell specialized cells bone marrow HSC
- 14. Challenges faced by stem cell research • Identifying stem cells in adult tissues. • Stem cell integration. • Immunological rejection. • Cancer. • Moral issues surrounding the sources of stem cells.
- 15. Thank You!
Notes de l'éditeur
- 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. 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. 2003 - Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth. 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. October 2006 - Scientists at Newcastle University in England create the first ever artificial liver cells using umbilical cord blood stem cells. 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.This may potentially provide an alternative to embryonic stem cells for use in research and therapy. June 2007 - Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer 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. 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",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":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 January 2008 - Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts 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. 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 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. 30 October 2008 - Embryonic-like stem cells from a single human hair. 1 March 2009 - Andras Nagy, Keisuke Kaji, et al. discover a way to produce embryonic-like stem cells from normal adult cells by using a novel "wrapping" procedure to deliver specific genes to adult cells to reprogram them into stem cells without the risks of using a virus to make the change.The use of electroporation is said to allow for the temporary insertion of genes into the cell. 05 March 2009 Australian scientists find a way to improve chemotherapy of mouse muscle stem cells. 09 March 2009 US President Obama lifted federal funding limits on human embryonic instituted by former President Bush.
- What is a stem cell? Note: The next slide provides an alternative version of this diagram that some younger audiences may find easier to understand. It aims to avoid the misconception that a stem cell always makes one copy of itself and one specialized cell when it divides (see below). The concept of a stem cell is very well explained in the short film, “A Stem Cell Story” at www.eurostemcell.org/films What the diagram shows Stem cells are different from other cells of the body because stem cells can both: Self-renew: Make copies of themselves AND 2) Differentiate: Make other types of cells – specialized cells of the body. ‘Specialized’ or ‘differentiated’ cells play particular roles in the body, e.g. blood cells, nerve cells, muscle cells. Specialized cells cannot divide to make copies of themselves. This makes stem cells very important. The body needs stem cells to replace specialized cells that die, are damaged or get used up. Cell division - possible questions 1) 16+ year old students may remember learning about 2 kinds of cell division – mitosis and meiosis. They may have learnt that mitosis happens in wound healing or to replace short-lived cells, but probably won’t have discussed stem cells in this context. You might therefore need to explain that most specialized cells cannot undergo mitosis. There are a few exceptions (e.g. liver cells or T-cells) but in general specialized cells can no longer divide. Skin cells, red blood cells or gut lining cells cannot undergo mitosis. Stem cells do divide by mitosis and this makes them very important for replacing lost or damaged specialized cells. 2) Should mitosis be discussed, you may wish to note the following: In mitosis, the DNA in the daughter cells is identical to the DNA in the dividing cell. This is true for dividing stem cells, both in self-renewal and in differentiation. In differentiation, the daughter cells are more specialized than the original stem cell. So, the daughter cells behave differently even though they have the same DNA as the stem cell. This is because there are lots of other molecules inside and around the cells that can change the way the cells behave. 3) Scientists think that when human stem cells divide they probably make EITHER two stem cells, OR two more specialized cells. In fruit flies, stem cells can divide to make one stem cell and one more specialized cell in a single division.
- Why self-renew AND differentiate? 1) Self renewal is needed because if the stem cells didn’t copy themselves, you would quickly run out. It is important for the body to maintain a pool of stem cells to use throughout your life. 2) Differentiation is important because specialized cells are used up, damaged or die all the time during your life. Specialized cells cannot divide and make copies of themselves, but they need to be replaced for your body to carry on working. For example, your body needs 100,000 million new blood cells every day. Of course, differentiation is also important for making all the different kinds of cell in the body during development of an embryo from a single fertilized egg. Possible questions or misconceptions 1) School students may have learnt simply that ‘cells undergo mitosis to make copies of themselves to heal wounds or replace blood cells’. You may need to explain that specialized cells like skin, red blood or gut cells cannot undergo mitosis, which is why you need stem cells. There are a few exceptions (e.g. liver cells or T-cells) but in general specialized cells can no longer divide. For adult audiences, this could be expanded to cover the idea that there are intermediate cells (progenitors) between stem cells and specialized cells that divide to allow a large number of new cells to be made (see slide 26 on renewing tissues) 2) Scientists think that stem cells in the human body don’t generally divide to produce one stem cell and one specialized cell at the same time. They probably divide to make EITHER two stem cells, OR two more specialized cells. In fruit flies, stem cells can divide to make one stem cell and one more specialized cell.
- Stem cell jargon Scientists use the words pluripotent and multipotent to help them describe stem cells. ALL stem cells can both self-renew and differentiate, BUT some stem cells can make more kinds of specialized cells than others. The terms on the slide are the key ones to remember. There are also stem cells that are: TOTIPOTENT: can differentiate into all types of specialized cells in the body PLUS cells that are needed during development of the embryo only: placenta, yolk sac, umbilical cord. UNIPOTENT: can only differentiate into one type of specialized cell. For example, spermatogonial stem cells (found in the testicles) are unipotent because they can only form sperm cells. A useful place to look up other words and phrases to do with stem cells is the EuroStemCell online glossary: www.eurostemcell.org/glossary
- Embryonic stem cells: What they can do Embryonic stem cells are exciting because they can make all the different types of cell in the body – scientists say these cells are pluripotent.
- Embryonic stem cells: Challenges Scientists around the world are trying to understand how and why embryonic stem cells produce skin, blood, nerve or any other particular kind of specialized cell. What controls the process so that the stem cells make the right amount of each cell type, at the right time? The big challenge for scientists is to learn how to control these fascinating cells. If we could force embryonic stem cells to make whatever kind of cell we want, then we would have a powerful tool for developing treatments for disease. For example, perhaps we could grow new insulin-producing cells to transplant into a patient with diabetes. But there is a great deal to learn before such therapies can be developed. Scientists also want to use stem cells to: Understand how diseases develop (disease modeling) Test drugs in the laboratory
- Tissue stem cells: Principles of renewing tissues The slide shows the typical hierarchy of cells from tissue stem cell to specialized cell. Stem cells give rise to committed progenitors. These are not fully differentiated cells but have different properties from stem cells – they are an intermediate cell type. Committed progenitors will divide many times and will give rise to fully differentiated and functional cells via a series of steps. This typical hierarchy is applicable to many types of tissue stem cell (some examples are given in the following slides to illustrate this principle).
- What are some advantages and disadvantages to stem cell therapy and research? It provides medical benefits in the fields of therapeutic cloning and regenerative medicine. It provides great potential for discovering treatments and cures to a plethora of diseases including Parkinson’s disease, schizophrenia, Alzheimer’s disease, Cancer, spinal cord injuries, diabetes and many more. Limbs and organs could be grown in a lab from stem cells and then used in transplants or to help treat illnesses. It will help scientists to learn about human growth and cell development. Scientists and doctors will be able to test millions of potential drugs and medicine, without the use of animals or human testers. This necessitates a process of simulating the effect the drug has on a specific population of cells. This would tell if the drug is useful or has any problems. Stem cell research also benefits the study of developmental stages that cannot be studied directly in a human embryo, which sometimes are linked with major clinical consequences such as birth defects, pregnancy loss and infertility. A more comprehensive understanding of normal development will ultimately allow the prevention or treatment of abnormal human development. It holds the key to reversing the effects of aging and prolonging our lives. Stem cell research has already found many treatments that help slow the aging process, and a bonus of further stem cell research is a possible ‘cure’ for aging altogether. The usage of adult stem cells to treat disease is that a patient’s own cells could be used to treat a patient. Risks would be quite reduced because patients’ bodies would not reject their own cells. An advantage of using embryonic stem cells is that they can develop into any cell types of the body, and may then be more versatile than adult stem cells. The use of embryonic stem cells for research involves the destruction of blastocysts formed from laboratory-fertilized human eggs. For those people who believe that life begins at conception, the blastocyst is a human life and to destroy it is immoral and unacceptable. Like any other new technology, it is also completely unknown what the long term effects of such an interference with nature could materialize. Embryonic stem cells may not be the solution for all ailments. According to a new research stem cell therapy was used on heart disease patients. It was found that it can make their coronary arteries become narrower. A disadvantage of most adult stem cells is that they are pre-specialized, for instance, blood stem cells make only blood, and brain stem cells make only brain cells. A disadvantage of embryonic stem cells is that they are derived from embryos that are not a patient’s own and the patient’s body may reject them.