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Stem Cell Presentation
- 1. Stem Cell Research NehaGupta and Regina Benson Slide 001
- 2. Stem Cells inthe News • "We still don't know what the deal is what that thing in Bush's back, but I tell you, if God has a sense of humor, it is something that can only be cured with stem cell research." -Bill Maher, on the bulge in Bush's back during the first presidential debate • "The reason the Democrats are so intent on passing a stem-cell bill is they're depending on the research to grow themselves a spine." Slide 003
- 3. Presentation Outline • Introductionto Stem Cell Science – Embryonic stem cell – Adult stem cells • Current Research • Current US & State Policies • Ethical Issues
- 4. Stem Cells Basics •Potential to develop into many different cell types in the body • Internal repair system in many tissues • Types of stem cells: -Embryonic stem cells -Somatic (adult) stem cells -Induced Pluripotent stem cells • Much work remains to be done in labs and clinics to understand how these cells can be used for cell-based therapies to treat disease
- 5. Producing embryonic stemcells • Source of embryonic stem cells – Derived from embryos of in vitro fertilized eggs with the informed consent of the donors – Derived from blastocysts • Stem cells are grown and subcultured for many months • Transcription factors regulate differentiation • Examining the chromosomes under microscope • Tests to identify human embryonic stem cell • Testing for pluripotency – Using Immunosuppression mouse model
- 6. Embryonic stem cellsstimulated to differentiate
- 7. Adult Stem CellsBasics • Undifferentiated cells found among differentiated cells in a tissue or organ • Primary role of adult stem cells is to maintain and repair the tissue where they are found • Origin of these stem cells in some mature tissues is still under investigation • Bone marrow has two kinds of stem cells: -Hematopoietic stem cells -Mesenchymal stem cells
- 8. Adult Stem CellDifferentiation
- 10. Stem Cell Media •Heart Tissue Generation Youtube video • Doctor injected MS sufferers with cow stem ce • Much work remains to be done in labs and clinics to understand how these cells can be used for cell-based therapies to treat disease
- 11. Examples of ClinicalResearch • Over 140 clinical trials are ongoing • Embryonic Stem Cells – Geron has FDA clearance to begin the first human clinical trial of embryonic stem cells for spinal cord injury • Adult Stem Cells – Stemedica has clearance for the treatment of ischemic stroke with bone marrow-derived stem cells (adult human)
- 12. US Legislation • LittleFederal Regulation • “Removing Barriers to Responsible Scientific Research Involving Human Stem Cells” – Signed March 9, 2009 by President Obama – Covered federal funding of stem cell research – Revoked two items from President Bush • The presidential statement of August 9, 2001 • Executive Order 13435 of June 20, 2007 • Set 3 criteria for funding • Stem cell research policy on a state level
- 13. State Legislation • Stemcell research policy on a state level – Most states neither permit or prohibit • States can also provide funding for research – Massachusetts funding - $1 Billion – California funding- $3 Billion
- 14. History of StemCell Legislation Modified from http://en.wikipedia.org/wiki/Stem_Cell_Research_Enhancement_Act
- 15. Recent Legal Case •Advocates International vs. Health and Human Services Secretary and director of the National Institute of Health – Violates Dickey-Wicker appropriations provision – Obama’s recent guideline funds unnecessary destruction of human embryos – Embryo discarded from IVF clinics are in need of “biological or adoptive parents” • Case was recently dismissed by US District Court Judge
- 16. Ethical Debate –Both Sides Arguments For Arguments Against Life does not begin until14 days after fertilization Alternatives like adult stem cells which have already produced a therapy are better An example is that when two individual twins come from an Embryo Researchers are halting the growth of blastocyst which is like taking away human’s life
- 17. Ethical Considerations • Adultstems cells are not an issue • Embryonic stem issues – When does human life begin? • Blastocyst? • Embryo? • Fetus?
- 18. Ethical and SocialIssues • How far should researchers take stem cell techniques? • Should the government provide funding for embryonic stem cell research? Why? Why not? • Should there be laws to regulate stem cell research? • Do embryonic stem cells represent a human life? • Should frozen embryos created through in vitro fertilization be used to create stem cells?
- 20. References • NIH Resourcefor Stem Cell Information – http://stemcells.nih.gov/info/health.asp • National Conference of State Legislation – http://www.ncsl.org/issuesresearch/health/embryonica ndfetalresearchlaws/tabid/14413/default.aspx • Stateline.org • International Society for Stem Cell Research http://www.isscr.org/public/regions/states.cfm#About
Editor's Notes
- #5 When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lung, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.
- #6 Source Growth & Subculturing Test ensure that the cells are capable of long-term growth and self-renewal. Two of the most important transcription factors are Nanog and Oct4. Transcription factors help turn genes on and off at the right time, which is an important part of the processes of cell differentiation and embryonic development. Both Oct 4 and Nanog are associated with maintaining the stem cells in an undifferentiated state, capable of self-renewal. Scientists inspect the cultures through a microscope to see that the cells look healthy and remain undifferentiated. This is a method to assess whether the chromosomes are damaged or if the number of chromosomes has changed. It does not detect genetic mutations in the cells. Testing for pluripotent by 1) allowing the cells to differentiate spontaneously in cell culture; 2) manipulating the cells so they will differentiate to form cells characteristic of the three germ layers; or 3) injecting the cells into a mouse with a suppressed immune system to test for the formation of a benign tumor called a teratoma. Since the mouse’s immune system is suppressed, the injected human stem cells are not rejected by the mouse immune system and scientists can observe growth and differentiation of the human stem cells. Teratomas typically contain a mixture of many differentiated or partly differentiated cell types—an indication that the embryonic stem cells are capable of differentiating into multiple cell types.
- #7 As long as the embryonic stem cells in culture are grown under appropriate conditions, they can remain undifferentiated (unspecialized). But if cells are allowed to clump together to form embryoid bodies, they begin to differentiate spontaneously. They can form muscle cells, nerve cells, and many other cell types. Although spontaneous differentiation is a good indication that a culture of embryonic stem cells is healthy. To generate cultures of specific types of differentiated cells such as heart muscle cells, blood cells, or nerve cells scientists try to control the differentiation of embryonic stem cells. They change the chemical composition of the culture medium, alter the surface of the culture dish, or modify the cells by inserting specific genes. Through years of experimentation, scientists have basic protocols or "recipes" for the directed differentiation of embryonic stem cells into some specific cell types. The differentiated embryonic stem cells may be able to treat certain diseases in the future. Diseases that might be treated by transplanting cells generated from human embryonic stem cells include Parkinson's disease, diabetes, traumatic spinal cord injury, Duchenne's muscular dystrophy, heart disease, and vision and hearing loss.
- #8 -hematopoietic stem cells, forms all the types of blood cells in the body. A second population, called bone marrow stromal stem cells (also called mesenchymal stem cells, or skeletal stem cells by some), were discovered a few years later. These non-hematopoietic stem cells make up a small proportion of the stromal cell population in the bone marrow, and can generate bone, cartilage, fat, cells that support the formation of blood, and fibrous connective tissue. In the 1960s, scientists who were studying rats discovered two regions of the brain that contained dividing cells that ultimately become nerve cells. Despite these reports, most scientists believed that the adult brain could not generate new nerve cells. It was not until the 1990s that scientists agreed that the adult brain does contain stem cells that are able to generate the brain's three major cell types—astrocytes and oligodendrocytes, which are non-neuronal cells, and neurons, or nerve cells.
- #9 -Normal differentiation pathways of adult stem cells. In a living animal, adult stem cells are available to divide, when needed, and can give rise to mature cell types that have characteristic shapes and specialized structures and functions of a particular tissue. The following are examples of differentiation pathways of adult stem cells (Figure 2) that have been demonstrated in vitro or in vivo. Hematopoietic stem cells give rise to all the types of blood cells: red blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes, and macrophages. Mesenchymal stem cells give rise to a variety of cell types: bone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and other kinds of connective tissue cells such as those in tendons. Neural stem cells in the brain give rise to its three major cell types: nerve cells (neurons) and two categories of non-neuronal cells—astrocytes and oligodendrocytes. Epithelial stem cells in the lining of the digestive tract occur in deep crypts and give rise to several cell types: absorptive cells, goblet cells, paneth cells, and enteroendocrine cells. Skin stem cells occur in the basal layer of the epidermis and at the base of hair follicles. The epidermal stem cells give rise to keratinocytes, which migrate to the surface of the skin and form a protective layer. The follicular stem cells can give rise to both the hair follicle and to the epidermis.
- #13 It is important to note that most laws affecting stem cell research where create for governing in vitro fertilization and abortion.. According to the International Society of Stem Cell Research there is little Federal Regulation of stem cell research. The most recent legislation related to stem cell research is an executive order signed on March 9, 2009 by President Barak Obama. The order published in the Federal Registrar was titled “Removing Barriers Responsible Scientific Research Involving Human Stem Cells.” This legislation describes the way the National Institute of Health can support stem cell research. It also revoked two of former President George W. Bush’s items on stem cell research. One was a Presidential statement given August 2001 and one was another Executive Order given in June of 2007. The Presidential statement given by G.W. Bush in 2001 made federal funding for stem cell research more difficult to obtain. It set three criteria to be meet in order to obtain research funding: Firstly, the derivation process (which begins with the destruction of the embryo) had to have been initiated prior to 9:00 P.M. on August 9, 2001. This means that no new stem cells could be derived and provide for research purposes, there were only 20 cell lines to work with and scientist had complained about their integrity. Second, the stem cells must have been derived from an embryo that was created for reproductive purposes, such as in vitro fertilization, and was no longer needed. Also, informed consent had to be obtained for the donation of the embryo and that donation could not involve financial incentives. Meaning, payment for embryonic stem cells to be used in research is not allowed. This was the policy until 2009, when Obama gave his executive order.
- #14 As you may see from the table, most states do not have legislation that permits or prohibits stem cell research. Massachusetts, California, New Jersey, Connecticut, Illinois, and Missouri currently have policies that permit stem cell research. In Massachusetts, a 2005 law established state policy to foster stem cell research and allows the donation of excess IVF embryos for research and created a biomedical research advisory committee. Democratic Governor Deval (approved in June 2008) a $1 billion (estimated to cost $66 Million for the UMAS Cell Bank) to support stem cell research and other life sciences; the program would establish research centers, fund university investigators, and establish a state stem cell repository. The 10-year initiative funds academic research and start-up companies, as well as create a stem cell bank at the University of Massachusetts for newly created lines of embryonic stem cells. The policy represents a marked shift in philosophy from the Romney administration, which injected language into a 2005 stem cell bill that would have barred scientists from using embryonic stem cells cloned for research purposes. The Legislature rebuffed Romney and passed a bill endorsing stem cell research, but provided no direct funding. The tendency for democratic, know to be liberal, to support stem cell research is clearly evident and Rebulicans have been seen as opposing or limiting funds and support policies to deter research efforts.
- #15 The Post article reported that although the Obama administration has lifted many of President George W. Bush's restrictions on federal funding for human embryonic stem cell research, some researchers are finding the new ethical requirements burdensome The 2005 and 2007 legislation would have increased access to government funding for scientist research stem cells. Both were veto by GW Bush. Obama has pending legislation that would increase access once passed. NIH Director Collins Defends Obama Administration Policy On Embryonic Stem Cell Research http://www.medicalnewstoday.com/articles/183284.php
- #16 The lawsuit charges that Obama’s recent executive order for expansion of funding for stem research violates former legislation regarding embryo research that prohibits federal funding of creating human embryos by any method, explicitly including human cloning, or any "research in which" human embryos are harmed in any way. http://www.lifenews.com/bio2930.html
- #18 The main question is if human life begins as a blastocyte, embryo, or fetus
- #19 Some ethical questions related to stem cell research.