PowerPoint PresentationSlide 2Slide 3Slide 4Slide 5Slide 6Slide 7Human development: a stem cell hierarchyDevelopmental hierarchies: the hematopoietic systemEmbryonic versus adultSlide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Cancer as a stem cell disease?Models of cancer cell growthExperimental evidence of cancer stem cellsSlide 25Stem Cells and CancerTHERAPEUTIC CLONINGORGANISM CLONINGNuclear transfer oocyteDonor cellNuclearTransfer Reproductive cloning BlastocystNT to create patient-specific ES cells Inner Cell MassCustomized patient-specificES cellG. DaleyPotential therapeutic uses of stem cells•Transplantation of bone marrow for muscular dystrophies•Direct injection of bone marrow stem cells for cardiac regeneration•Bone marrow injections for neurodegenerative diseasesWhat are stem cells? Units of development and regenerationStem cellDifferentiated cellLiver, blood, nerveQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.What 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 potentialHSCThymusT cellsB cellsNK cellsNeutrophilEosinophilErythrocyteMegakaryocyteMast cellMacrophageDifferentiationDevelopmental potentialDevelopmental hierarchies: the hematopoietic systemEmbryonic versus adult•Isolated from early embryos•Can expand indefinitely in culture•Can give rise to all cell types•Isolated from adult human tissue•Can not be expanded in culture•Can only give rise to same tissueNuclear transfer oocyteDonor cellNuclearTransfer Reproductive cloning BlastocystNT 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 INDEVELOPMENTQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.CH35- methylcytosineDNA IS MODIFIED DURING DEVELOPMENTQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.IN HUMAN FEMALES ONE X INACTIVATED IN DEVELOPMENTQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.Nuclear transfer oocyteDonor cellNuclearTransfer Reproductive cloning BlastocystNT to create patient-specific ES cells Inner Cell MassCustomized patient-specificES cellG. DaleyQuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.Embryonic Stem (ES) Cells––> Mice derived from Cultured CellBlastocyst (brown)Host blastocyst(black)Embryo transferChimeric founderCell injectionRudolf JaenischPotential therapeutic uses of stem cells•Transplantation of bone marrow for muscular dystrophies•Direct injection of bone marrow stem cells for cardiac regeneration•Bone marrow injections for neurodegenerative diseasesNuclear transfer oocyteDonor cellNuclearTransfer Reproductive cloning BlastocystNT 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 morphologically heterogeneousModels of cancer cell growthStochastic Model Cancer Cancer CancerStem Cell ModelCancer NORMALExperimental evidence of cancer stem cells•Acute myeloid leukemia: CD34+ CD38neg cells are tumor initiating (only 0.1% of total tumor cells)•Breast cancer: CD44+CD24neg (2% of all tumor cells)•Brain cancer: CD133+ (~20% of all tumor cells)QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this
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