1Stem Cells and CancerTHERAPEUTIC CLONINGORGANISM CLONINGNuclear transfer oocyteDonor cellNuclearTransfer Reproductive cloningBlastocystNT to create patient-specific ES cells Inner Cell MassCustomized patient-specificES cellG. DaleyPotential therapeutic uses of stem cells• Transplantation of bone marrow formuscular dystrophies• Direct injection of bone marrow stem cellsfor cardiac regeneration• Bone marrow injections forneurodegenerative diseases2What are stem cells? Units of development and regenerationStem cellDifferentiated cellLiver, blood, nerveWhat are stem cells? Units of development and regenerationWhy are stem cells unique? 1. They are unspecialized2. The can produce more stem cells3. They can produce specialized cellsLiverGutPancreasBloodMuscleBoneNervous systemSkinDifferentiationHuman development: a stem cell hierarchyEndodermMesodermEctodermEmbryonic stem cellsDevelopmental potential3HSCThymusT cellsB cellsNK cellsNeutrophilEosinophilErythrocyteMegakaryocyteMast cellMacrophageDifferentiationDevelopmental potentialDevelopmental hierarchies:the hematopoietic systemEmbryonic versus adult• Isolated from earlyembryos• Can expandindefinitely in culture• Can give rise to allcell types• Isolated from adulthuman tissue• Can not beexpanded in culture• Can only give rise tosame tissueNuclear transfer oocyteDonor cellNuclearTransfer Reproductive cloningBlastocystNT to create patient-specific ES cells Inner Cell MassCustomized patient-specificES cellG. DaleyWHY ORGANISM CLONING MIGHT NOT WORK1. TECHNICAL REASONS---2. GENES OR CHROMOSOMES ARE LOST OR CHANGED INDEVELOPMENT4CH35- methylcytosineDNA IS MODIFIED DURING DEVELOPMENTIN HUMAN FEMALES ONE X INACTIVATED IN DEVELOPMENTNuclear transfer oocyteDonor cellNuclearTransfer Reproductive cloningBlastocystNT to create patient-specific ES cells Inner Cell MassCustomized patient-specificES cellG. Daley5Rudolf JaenischPotential therapeutic uses of stem cells• Transplantation of bone marrow formuscular dystrophies• Direct injection of bone marrow stem cellsfor cardiac regeneration• Bone marrow injections forneurodegenerative diseases6Nuclear transfer oocyteDonor cellNuclearTransfer Reproductive cloningBlastocystNT to create patient-specific ES cells Inner Cell MassCustomized patient-specificES cellG. DaleyCancer as a stem cell disease?• Low clonogenic ability of tumors in vitro• Most tumors are morphologicallyheterogeneousModels of cancer cell growthStochastic Model Cancer Cancer CancerStem Cell ModelCancer NORMALExperimental evidence ofcancer stem cells• Acute myeloid leukemia: CD34+ CD38neg cellsare tumor initiating (only 0.1% of total tumorcells)• Breast cancer: CD44+CD24neg (2% of all tumorcells)• Brain cancer: CD133+ (~20% of all tumor
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