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- 2. History of Adult Stem Cell Research Since the 1970’s, bone marrow transplants have been used for treatment of Immunodeficient and leukemia.
- 3. History of Human Embryonic Stem Cell Research Isolate inner cell mass Culture cells Inner cell mass (forms fetus) Day 5-6 Blastocyst
- 4. In 1998, James Thomson (University of Wisconsin- Madison) isolated cells from the inner cell mass of the early embryo, and developed the first human embryonic stem cell lines, History of Human Embryonic Stem Cell Research In 1998, John Gearhart (Johns Hopkins University) derived human embryonic germ cells from cells in fetal gonadal tissue (primordial germ cells). Pluripotent stem cell “lines” were developed from both sources
- 5. What Are Stem Cells? Stem cells are the raw material from which all of the body’s mature, differentiated cells are made. Stem cells give rise to brain cells, nerve cells, heart cells, pancreatic cells, etc.
- 6. Stem Cell – Definition A cell that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues
- 7. Stem Cell – are Dynamic Are undifferentiated “master” cell that do not yet have a specific function Can change to one or several different cell types (differentiate) under proper conditions Can undergo unlimited cell division, self-renewal) Stem cell Stem cell S e l f - r e n e w a l Specialized cell (e.g., white blood cell) D i f f e r e n t i a t e
- 8. One Cell - Several lineages
- 9. Embryogenesis and Differentiation Specific regions of the embryo give rise to the specific organ systems Ectoderm generates the outer layer of the embryo and produces the surface layer (epidermis) of the skin and forms the nerves Endoderm becomes the innermost layer of the embryo and produces the digestive tube and its associated organs (including the lungs) Mesoderm becomes sandwiched between the ectoderm and endoderm and generates the blood, heart, kidney, gonads, bones, and connective tissues.
- 11. An Overview of Early Development modeled with Play-Dough Fertilized egg Totipotent stem cells Totipotent: Can become any cell in body or placenta Fate Decision Pluripotent stem cells (3-5 days old) Blastocyst Pluripotent: Can become any cell in body Implantation Fate Decision Gastrulation (day 14) leads to Primary Germ Cells Endoderm (inner)digestive tract, resp. track Mesoderm (middle)bones, blood cells, heart Ectoderm (outer)skin, CNS Multipotent: Can become any cell within a specific germ layer or cell lineage Embryonic stem cells come from inner cell mass of blastocyst. Implantation Fate Decision Gastrulation (day 14) leads to Primary Germ Cells Endoderm (inner)digestive tract, resp. track Mesoderm (middle)bones, blood cells, heart Ectoderm (outer)skin, CNS Multipotent: Can become any cell within a specific germ layer or cell lineage Multipotent
- 13. Somatic Cell Endoderm Ectoderm Mesoderm Liver Intestine Pancreas Skin Hair Nerves Blood Muscle Bone Cartilage Somatic stem cell Germ stem cell Primitive germ cell Gametes Pluripotent Embryonal stem cell Totipotent stem cells Pluripotent stem cells Adult Multipotent stem cell Courtesy of Dr F. Prosper Cardoso.
- 14. Bone Marrow Stem Cells
- 15. How to Derive an Embryonic Stem Cell Line? Inner cell mass Day 5-6 Blastocyst Isolate inner cell mass (destroys embryo) ETHICS? Culture cells A stem cell line is composed of a population of cells that can replicate themselves for long periods of time in vitro (out of the body) An embryonic stem cell clone
- 16. The Science of Stem Cells Stem cells have the ability to continually reproduce themselves while maintaining the capacity to give rise to other more specialized cells. Stem cells are found at all stages of development, from embryonic stem (ES) cells that can differentiate into all specialized cells found in the human body, to adult stem cells capable of regenerating their tissue of origin. Stem cells occur from the earliest stages of development and provide the starting material for every organ and tissues.
- 17. Embryonic stem (ES) cells ES cells are found at the blastocyst stage, four to five days after the union of the sperm and egg, before the embryo implants in the uterus.
- 19. Source of Stem cells Stem cells may be derived from autologus, allogeneic or xenogenic sources. Histocompatability is prerequisite for transplantation of allogeneic stem cells. Fatal tissue is the best current tissue source for human neural stem cells, however ethical issues are a major concern.
- 20. Placenta a Source of Stem Cells Placental stem cells, like umbilical cord blood and bone marrow stem cells, can be used to cure chronic blood-related disorders such as sickle cell disease, Thalasemia, and leukaemia.
- 21. Umbilical Cord Blood Stem Cell Transplant Umbilical cord blood stem cell transplants are less prone to rejection than either bone marrow or peripheral blood stem cells. This is probably because the cells have not yet developed the features that can be recognized and attacked by the recipient's immune system
- 22. Kinds of Stem Cells Stem cell type Stem cell type Description Description Examples Examples Totipotent Totipotent Each cell can develop into a Each cell can develop into a new individual new individual Cells from early (1-3 Cells from early (1-3 days) embryos days) embryos Pluripotent Pluripotent Cells can form any (over 200) Cells can form any (over 200) cell types cell types Some cells of Some cells of blastocyst (5 to 14 blastocyst (5 to 14 days) days) Multipotent Multipotent Cells differentiated, but can Cells differentiated, but can form a number of other form a number of other tissues tissues Fetal tissue, cord Fetal tissue, cord blood, and adult stem blood, and adult stem cells cells
- 23. What’s So Special About Stem Cells? • They have the potential to replace cell tissue that has been damaged or destroyed by severe illnesses. They can replicate themselves over and over for a very long time. Understanding how stem cells develop into healthy and diseased cells will assist the search for cures.
- 24. Two Kinds of Stem Cells • Embryonic (also called “pluripotent”) stem cells are capable of developing into all the cell types of the body. • Adult stem cells are less versatile and more difficult to identify, isolate, and purify.
- 25. Stages of Embryogenesis Day 1 Fertilized egg Day 2 2-cell embryo Day 3-4 Multi-cell embryo Day 5-6 Blastocyst Day 11-14 Tissue Differentiation
- 26. Derivation and Use of Embryonic Stem Cell Lines Isolate inner cell mass (destroys embryo) Heart muscle Kidney Liver “Special sauce” (largely unknown) Day 5-6 Blastocyst Inner cells (forms fetus) Outer cells (forms placenta) Heart repaired Culture cells
- 27. Embryonic Stem Cells: Researchers extract stem cells from a 5-7 days old Researchers extract stem cells from a 5-7 days old blastocyst blastocyst. . Stem cells can divide in culture to form more of their own kind, Stem cells can divide in culture to form more of their own kind, thereby creating a stem cell line. thereby creating a stem cell line. The research aims to induce these cells to generate healthy tissue needed by patients.
- 28. How Many Human Embryonic Stem Cell Lines are There? The actual number of human embryonic stem cell lines is a matter of some debate. To date, more than 100 human embryonic stem cell lines have been derived worldwide. However, most of those lines are not adequately characterized yet. Only 22 cell lines are eligible for federal funding in the USA.
- 29. Autologous – Stem Cells Sources of the patient's own stem cells (autologous) are either the cells from patient's own body or his or her cord blood. For autologous transplants physicians now usually collect stem cells from the peripheral blood rather than the marrow This procedure is easier, unlike a bone marrow harvest, it can take place outside of an operating room and the patient does not have to be under general anaesthesia.
- 30. Allogeneic – Stem Cells Sources of stem cells from another donor (allogeneic) are primarily relatives (familial-allogeneic) or completely unrelated donors (unrelated- allogeneic). The stem cells in this situation are extracted from either the donor's body or cord blood
- 31. Xenogenic - Stem Cells In this stem cells from different species are transplanted, e.g. striatal porcine fetal ventral mesencephalic (FVM) xenotransplants for Parkinson's disease. This has no major ethical concerns and a large amount of tissue is available, however life long immunosupression and risk of rejection are the major limitations
- 32. How Does Cell Therapy Work? Stem cells can be used to generate healthy and functioning specialized cells, which can then replace diseased or dysfunctional cells. It is similar to the process of organ transplantation only the treatment consists of transplanting cells instead of organs.
- 33. How Does Cell Therapy Work? Bone marrow transplants are an example of cell therapy in which the stem cells in a donor's marrow are used to replace the blood cells of the victims of leukemia. Cell therapy is also being used in experiments to graft new skin cells to treat serious burn victims, and to grow new corneas for the sight-impaired. In all of these uses, the goal is for the healthy cells to become integrated into the body and begin to function like the patient's own cells.
- 34. What Diseases Can be Cured by Stem Cell Therapies Any disease in which there is tissue regeneration can be a potential candidate for stem cell therapies
- 35. Major Progress in Several Important Health problems Alzheimer’s disease Parkinson’s disease Spinal cord injury Heart disease Severe burns Diabetes
- 36. Alzheimer’s disease and can stem cells help? Stem cells could, however, be genetically modified so as to deliver substances to the Alzheimer brain, to stop cells from dying and stimulate the function of existing cells. A recent clinical trial (Phase I) has shown this approach to be of some benefit to patients with Alzheimer’s disease, by slowing down the progression of the disease.
- 37. Drug Testing Stem cells could allow scientists to test new drugs using human cell line which could speed up new drug development. Only drugs that were safe and had beneficial effects in cell line testing would graduate to whole animal or human testing. It would allow quicker and safer development of new drugs.
- 38. Major types of Stem Cells 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. I
- 39. Stem Cell Research Worldwide
- 40. Adult Stem Cells
- 41. Autologus – Stem Cells While most blood stem cells reside in the bone marrow, a small number are present in the bloodstream. These multipotent peripheral blood stem cells, or PBSCs, can be used just like bone marrow stem cells to treat leukaemia, other cancers and various blood disorders
- 43. Applications of Stem Cells Cell Replacement Therapies Cells could be stimulated to develop into specialized cells that represent renewable sources of cells and tissue for transplantation. Cell replacement therapy could treat injuries and various genetic and degenerative conditions including muscular dystrophies, retinal degeneration, Alzheimer disease, Parkinson's disease, arthritis, diabetes, spinal cord injuries, and blood disorders such as hemophilia.
- 44. Understanding Cell Specialization Studying human pluripotent stem cells can lead to the identification of factors responsible for differentiation of stem cells into specialized cell types. these factors may ultimately be used to drive tissue regeneration and repair if administered therapeutically. This work will provide basic knowledge on cell determination and differentiation, human development, genomic imprinting and somatic cell aging.
- 45. Limbal stem Cell therapy The treatment is known as limbal stem cell therapy, and the patients who received the treatment suffered from chemical burn or genetic disease know as aniridia By replacing the limbal stem cells, the cornea begins to clear up as the cells are replaced with the healthy transparent layer again.
- 46. Obstacles of Stem Cell Research How to find the right type of stem cells? How to put the stem cells into the right place? Will the stem cells perform the desired function in the body? Differentiation protocols for many cell types have not been developed.
- 47. Embryonic Stem Cells are Unstable and Mutate in Culture Like ordinary cells, stem cells accumulate significant numbers of mutations over time, including several that could cause them to become tumors.
- 48. Ethical debate Harvesting ES cells destroys the blast cyst “This is murder” ES cell research requires human cells Could create a commercial market for human cells “This devalues life” Reproduced by permission of Dave Catrow and Copley News Service
- 49. Destroying life to cure some one – Ethical ? If stem cells have such potential to relieve suffering, why are so many people so upset about their use? The reason is that the most powerful type of stem cell embryonic stem � (ES) cells can only be obtained from � human embryos. Many people think that it's wrong to create and destroy human embryos to treat disease
- 50. Religious Debate over Harvesting Embryonic Stem Cells The pro-life group generally believes that: Personhood happens at, or shortly after, conception. Thus, they consider the removal of stem cells from an embryo -- a procedure which kills the stem cells -- to be a form of murder of a human being. They argue that no potential health benefits to even hundreds of millions of people can justify the murder of other humans. Day 5-6 Blastocyst
- 51. Religious Debate over Harvesting Embryonic Stem Cells The pro-choice group generally believes that: Personhood is attained much later in pregnancy, perhaps when the fetal brain develops consciousness during the third trimester. Thus, extracting stem cells from an five or ten-day old pre-embryo is not murder. Killing a pre-embryo, which is only a potential human being, is justified if it has the potential to cure diseases and extend the lives of people. Day 5-6 Blastocyst
- 53. Shall be Clone Humans ? Arguments for and against human cloning research. Should we ban human cloning? Why investors are moving away from human cloning and why human cloning now looks a last- century way to fight disease. Why some people want to clone themselves or even to clone the dead.
Editor's Notes
- #2: Adult stem cell research on humans began in the 1960's, first achieving success in the treatment of a patient with severe combined immunodeficiency disorder in 1968. Since the early 1970's, adult stem cells have been successfully used for treatment of immunodeficiencies and leukemias.
- #4: Human embryonic stem cells were first isolated in 1998. The cells from these embryos were established as immortal pluripotent cell lines that are still in existence today.
- #6: Stem cells are different from other cells of the body in that they have the ability to differentiate into other cell/tissue types. This ability allows them to replace cells that have died. With this ability, they have been used to replace defective cells/tissues in patients who have certain diseases or defects.
- #14: Stem cells from bone marrow form a number of cell types of the immune and circulatory system. These stem cells have been used to cure diseases since the 1960's.
- #15: The inner cell mass (the part that would form the fetus) of the embryo is isolated and disrupted to form embryonic cell lines. This process destroys the embryo. Under special culture conditions, the cells of the embryonic lines can be coaxed to form certain kinds of differentiated cell types. In theory, these differentiated cells could be used to repair or replace defective cells or tissues.
- #22: Stem cells can be classified into three broad categories, based on their ability to differentiate. Totipotent stem cells are found only in early embryos. Each cell can form a complete organism (e.g., identical twins). Pluripotent stem cells exist in the undifferentiated inner cell mass of the blastocyst and can form any of the over 200 different cell types found in the body. Multipotent stem cells are derived from fetal tissue, cord blood and adult stem cells. Although their ability to differentiate is more limited than pluripotent stem cells, they already have a track record of success in cell-based therapies. Here is a current list of the sources of stem cells: Embryonic stem cells - are harvested from the inner cell mass of the blastocyst seven to ten days after fertilization. Fetal stem cells - are taken from the germline tissues that will make up the gonads of aborted fetuses. Umbilical cord stem cells - Umbilical cord blood contains stem cells similar to those found in bone marrow. Placenta derived stem cells - up to ten times as many stem cells can be harvested from a placenta as from cord blood. Adult stem cells - Many adult tissues contain stem cells that can be isolated.
- #25: The early stages of embryogenesis are the point at which embryonic stem cell lines are derived. The fertilized egg (day 1) undergoes cell division to form a 2-cell embryo, followed by 4-cell, etc. until a ball of cells is formed by the fourth day. The ball becomes hollow, forming the blastocyst. This is the stage at which pluripotent embryonic stem cell lines are generated. Following the blastocyst stage, the tissues of the embryo start to form and the cells become multipotent.
- #26: The inner cell mass (the part that would form the fetus) of the embryo is isolated and disrupted to form embryonic cell lines. This process destroys the embryo. Under special culture conditions, the cells of the embryonic lines can be coaxed to form certain kinds of differentiated cell types. In theory, these differentiated cells could be used to repair or replace defective cells or tissues.
- #48: ES cell research is a very controversial topic. The main issue is the moral status of a human embryo. Is it ethical to destroy an embryo in order to save a patient’s life? This isn’t the only issue raised by ES cells. Even if you believe that it is ethically acceptable to destroy human embryos, other issues arise. This section of the presentation uses cartoons to introduce some of the basic ethical issues surrounding ES cell research. ES cell research involves the destruction of embryos. The destruction of the embryo happens when the ES cells are harvested from the ICM. Some people believe that an embryo contains a human life. For them, killing an embryo is equivalent to murder. Notice that the artist represents the embryo in this cartoon as a miniature baby. People who hold this position often point out that AS cells, whose derivation does not entail the destruction of embryos, may be able to provide the same life-saving benefits of ES cells. They argue that ES cell research is not only wrong--it is unnecessary.