Stem Cells and Cancer THERAPEUTIC CLONING ORGANISM CLONING NT to create patient specific Reproductive cloningES cells Nuclear transfer oocyte Donor cell Nuclear Transfer Customized patient specific ES cell Inner Cell Mass Blastocyst G Daley Potential 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 diseases What are stem cells Units of development and regeneration Stem cell Differentiated cell Liver blood nerve QuickTime and a TIFF Uncompressed decompressor are needed to see this picture QuickTime and a TIFF Uncompressed decompressor are needed to see this picture QuickTime and a TIFF Uncompressed decompres are needed to see this picture What are stem cells Units of development and regeneration Why are stem cells unique 1 They are unspecialized 2 The can produce more stem cells 3 They can produce specialized cells Human development a stem cell hierarchy Differentiation Endoderm Mesoderm Ectoderm Liver Gut Pancreas Blood Muscle Bone Nervous system Skin Embryonic stem cells Developmental potential Differentiation Developmental hierarchies the hematopoietic system Developmental potential Thymus T cells NK cells B cells HSC Neutrophil Macrophage Eosinophil Erythrocyte Megakaryocyte Mast cell Embryonic 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 tissue NT to create patient specific Reproductive cloningES cells Nuclear transfer oocyte Donor cell Nuclear Transfer Customized patient specific ES cell Inner Cell Mass Blastocyst G Daley WHY ORGANISM CLONING MIGHT NOT WORK 1 TECHNICAL REASONS 2 GENES OR CHROMOSOMES ARE LOST OR CHANGED IN DEVELOPMENT DNA IS MODIFIED DURING DEVELOPMENT CH 3 QuickTime and adecompressor TIFF are Uncompressed needed to see this picture 5 methylcytosine IN HUMAN FEMALES ONE X INACTIVATED IN DEVELOPMENT QuickTime and a TIFF Uncompressed decompressor are needed to see this picture QuickTime and a TIFF Uncompressed decompressor are needed to see this picture NT to create patient specific Reproductive cloningES cells Nuclear transfer oocyte Donor cell Nuclear Transfer Customized patient specific ES cell Inner Cell Mass Blastocyst G Daley QuickTime and a TIFF Uncompressed decompressor are needed to see this picture QuickTime and a TIFF Uncompressed decompressor are needed to see this picture Embryo Cell injection transfer Chimeric Host Blastocyst blastocyst founder Mice derived from Embryonic Stem ES Cells brown black Cultured Cell Rudolf Jaenisch Potential 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 diseases NT to create patient specific Reproductive cloningES cells Nuclear transfer oocyte Donor cell Nuclear Transfer Customized patient specific ES cell Inner Cell Mass Blastocyst G Daley Cancer as a stem cell disease Low clonogenic ability of tumors in vitro Most tumors are morphologically heterogeneous Models of cancer cell growth Stochastic Model Cancer Cancer Cancer Stem Cell Model Cancer NORMAL Experimental 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 andTIFF a QuickTime and decompressor a TIFF Uncompressed decompressor Uncompressed are needed to see thisare picture needed to see this picture
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