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Stem Cells and Animal Cloning 5. Stem Cell Research 1. Human Genome Project 2. Genetic Testing 6. Animal Cloning 20-week fetus in utero. 3. Genetic Engineering 4. ARTs Stem cells are essentially undifferentiated cells… They can become many different kinds of cells A stem cell must be able to do the following: 1. Produce specialized descendants 2. Retain ability to reproduce themselves Two Classes of Stem Cells A. Totipotent stem cells Give rise to all cell types Embryonic Stem Cells: derived from the inner cell mass of the blastocyst. Cannot give rise to an individual organism B. pluripotent stem cells Give rise to several specialized cell types Adult Stem cells Adult Stem cells are used by the body to repair and regenerate damaged organs and tissues throughout life. From where stem cells are isolated All adult cells including adult stem cells come from one of 3 cell lineages: 1. Endoderm 2. Ectoderm 3. Mesoderm Adult Stem Cells 1. Blood Stem Cells: Hematopoietic cells are found in the bone marrow and give rise to all red and white blood cells 2. Mesenchymal Cells: give rise to new bone, cartilage, and connective tissue 3. Neuronal Stem Cells: nervous system tissue (mostly produced during embryonic development) pluripotent Blood Stem Cell gives rise to many different cell types Adult Tissues and Organs Known To Have Stem Cells • Brain: can become 3 kinds of nerve cells and even some blood cells • Skin: replace all types of skin cells • Bone Marrow: Blood, bone and cartilage • Endothelium: Blood vessels and cardiomyocytes • Skeletal Muscle: muscle growth • Digestive System: Epithelial lining of the gut • Pancreas: pancreatic β cells • Liver: stem cells from bone marrow may repair the liver The Promise of Adult Stem Cells • 1. 2. 3. Advantages: Can be used to cure some diseases Directed differentiation possible If isolated from the same patient, no tissue rejection issues 4. No ethical issues • Disadvantages: 1. Limited use 2. Currently difficult to isolate (except for bone marrow) Growing Body Parts From Cell Cultures • Biojewellry: Wedding rings grown from each others bones! • http://www.biojewelry.co.uk Bone cell culture from a cow, inlaid with silver In contrast, embryonic stem (ES) cells are not limited in their potential to become every cell type. It is the versatility of these cells that gives them the potential to have more therapeutic applications than adult stem cells Stem Cells • Embryonic stem cells are the precursors to all more specialized stem cells • They are found in the inner cell mass of the blastocyst • 1998 the first culture of embryonic stem cells maintained in the laboratory Biology of Embryonic Stem Cells • Blastocyst is made of the trophoblast and the inner cell mass • There is no way to remove the ICM without killing the embryo • Once the ICM is separated from the trophoblast, the embryo can no longer develop into a fetus • Directed Differentiation – Requires the trophoblast – Otherwise, the ICM is like a child who has lost its way home, with no map to guide them – Requires growth factos and hormones to coax cell in to becoming specialized tissues Source of Embryonic Stem Cells • Obtained from IVF (In Vitro Fertilization) clinics • Ethical issues – Is it ever OK to use human embryos? – When is it OK to use human embryos? – What is done with all the frozen embryos not used for implantation? Cardiomyocyte differentiated from human embryonic stem cells. Stem Cell Therapy • Most stem cell therapies are in the research stage with mice and rats • Treatments for humans would include: • Leukemia (using patients bone marrow) • Diabetes: a “cure” vs treatment (using patients adult stem cells to create a population of cells that produce insulin) • Cardiovascular disease: injecting stem cells into the patient • Neurological disorders: – – – – – Alzheimers Tay-Sachs Huntington’s Chorea Spinal Chord injuries Parkinsons • Organ Factories? • The problem of immune rejection depends on the source of the stem cells • Adult Stem Cell therapy: – Not easy to isolate – Unknowns in regard to repair of neural tissue • Memory retention • Psychology • Umbilical Chord Stem Cells (UCS): – Can replace bone marrow transplants – Successfully used to treat leukemia in humans • Growth Factors: might also cause cancers • Wandering Stem Cells: Will stem cells always go where they are intended? • Stem Cell Cancer Induction Reality Check Animal Cloning: Species that have been cloned • • • • • • Cattle Goats Pigs Cat (CC the Copy Cat) Sheep (Dolly) Deer (Dewey) Methods used to clone animals Nuclear transfer (SCNT) Somatic Cell Nuclear Transfer (SCNT) • First done in 1951 with frogs • The mystery of development and differentiation from a single endowment of DNA • The principle of Nuclear equivalence – Nuclei of all cells are genetically identical – But, different cells express different subsets of genes • Somatic cells • Germ line cells – Totipotency • Capability of cells to direct development of entire organism – Can pre-programmed chromosomes be used for cloning whole organisms? Somatic Cell Nuclear Transfer SCNT • uses unfertilized eggs • nucleus is removed from the egg • nucleus from a donor cell is injected Empty Egg Seeks Nucleus for LTR • Source of Nucleus is important: – Embryonic stem cells: unprogrammed; cloning blindly – Adult cells: programmed • know the characteristics • “shop before you buy” How Dolly was made: What happened to Dolly? • The main problems associated with cloning animals from adult cells: 1. cloned lambs with immature lungs 2. deformed kidneys 3. hearts with thickened walls and 4. skeletal abnormalities Cloning Pets • Reproductive Cloning: Cloning to produce an individual • Genetic Savings and Clone – gene banking and cloning of exceptional pets http://www.savingsandclone.com/ • PerPETuate Inc. – http://www.perpetuate.net/ Reproductive Cloning: When cloning results in an organism Gizmo and Little Gizmo Mango and Peaches Therapeutic Cloning Creating tissues and organs for individuals • Requires a nucleus from YOU and an enucleated egg cell (SCNT) • Grow embryonic stem cells that are genetically identical to the individual. The cells are grown into tissue for repair of damaged organs • It would create “perfect-match” tissue. No more tissue rejection issues. • Is generating a few cloned embryonic cells for tissue repair from an adult the same as using a zygote from invitro fertilization? Therapeutic Cloning vs. Reproductive Cloning • Adult stem cell research (no problem) • Embryonic stem cell research – IVF embryos – Therapeutic cloning • Reproductive Cloning is relegated to the cloning of non-human animals Those opposed to stem cell research • Opposed to the use of Embryonic stem cells • Research underway to reprogram adult cells for tissue repair so that they can be as versatile as ES.