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Stem cellsWhat makes a stem cell a stem cell?• Stem cells can divide without limit• Stem cells are visibly undifferentiated• Stem cells’ progeny include both further stemcells and cells destined to differentiateStem cells’ progeny include bothfurther stem cells and cells destined todifferentiateStem cellsEmbryonic(Sources:MorulaBlastocystFetus’ germ cells)Adult(Sources:Renewing tissues,Umbilical cord)Embryonic stem cells• Similar to and derived from the mammalianembryonic epiblast or Inner Cell Mass (ICM)• Capable of forming any cell type in the body ifreimplanted into an embryoAdult Stem Cells (tissue stem cells)• Are found in renewal tissues of the adult(skin, intestine, bone marrow)• Are usually committed to form one particulartissue type (skin, keratinocytes, intestinalcells, blood and lymph cells)Sources of Embryonic Stem CellsGerm cells fromspontaneouslyaborted fetusesLeft-over embryosfrom In VitroFertilizationAdult stem cells and TherapeuticcloningStillexperimentalHumancloning, notstem cellresearchAdult Stem Cells• Cell growth is confined to the renewingtissues: skin, blood, intestine, etc.• In the adult, cell division is under tightinhibitory control. Stem cells can survive onlyin special niches, where they receive factorsthat will prevent their death and control theirdifferentiation• Stem cell niche - a microenvironment suitablefor the survival and growth of the stem cells.Hematopoietic Stem Cells (HSC) give rise to anincredible variety of blood and lymph cells: redblood (oxygen carrier) cells, leukocytes (innateimmunity) cells, lymphocytes (T-cells and B-cells, adaptive immunity)Erythrocytes (redblood cells)plateletsLeukocytes(white blood cellsSEM of Human bloodHematopoietic Stem Cells (HSC) lineageBlood cell precursorlymphocyte precursorInterleukin 3 andStem Cell Factor(SCF)HSC’s can becultured in vitro, byplating bone marrowcells on soft agar ormethyl cellulose.Differentcombinations ofhematopoietic growthfactors will stimulatedifferentiation intodifferent lineages.Hematopoietic Stem Cell Niche: bonemarrow. Used in 40,000 transplants/year.Most sensitive to irradiationCritical forself-renewalPotential pluriipotent adult stem cells(still at a very early stage of research)• Mesenchymal stem cells (bone marrow) -blood cells, neural cells, endodermal cells,can integrate into ICM• Umbilical cord stem cells - when cultured indifferent media, can differentiate intocartilage, liver cells, neurons.Potential benefits of human stem cells• Production of new neurons for patients withdegenerative brain disorders (Alzheimer,Parkinson) or spinal cord injuries• Production of healthy pancreas for diabetespatients• Re-population of blood and lymph cells forcancer patients with damaged or absent bonemarrow or other patients with immunedeficienciesBasic scientific problems to overcomein the stem cell research• How to direct differentiation of cellsdown specific pathways (e.g. muscle,nerve - different coctails of growthfactors?• How to overcome immune rejection?• How to make an organ? (e.g. growdifferent cell type in a 3-D functionalstructure)• …most scientists, at least today, believe that research on embryonic stem cells offer themost promise because these cells have the potential to develop in all of the tissues in thebody.• Scientists further believe that rapid progress in this research will come only withfederal funds. Federal dollars help attract the best and brightest scientists. They ensurenew discoveries are widely shared at the largest number of research facilities and that theresearch is directed toward the greatest public good.• The United States has a long and proud record of leading the world toward advancesin science and medicine that improve human life. And the United States has a long andproud record of upholding the highest standards of ethics as we expand the limits ofscience and knowledge. Research on embryonic stem cells raises profound ethicalquestions, because extracting the stem cell destroys the embryo, and thus destroys itspotential for life. Like a snowflake, each of these embryos is unique, with the uniquegenetic potential of an individual human being.• As I thought through this issue, I kept returning to two fundamental questions: First,are these frozen embryos human life, and therefore, something precious to be protected?And second, if they're going to be destroyed anyway, shouldn't they be used for a greatergood, for research that has the potential to save and improve other lives?President G. W. Bush (2001)Embryonic Stem Cells DebateWhat type/s of research should besupported by federal funds?A. Adult stem cells, umbilical cord stemcells.B. A + the 21 pre-existing embryonicstem cells linesC. A + embryonic stem


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UCSD BICD 130 - Stem Cells

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