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Stem Cells and Cancer THERAPEUTIC CLONING ORGANISM CLONING NT to create patient specific Reproductive cloningES cells Nuclear transfer oocyte Donor cell Potential therapeutic uses of stem cells Transplantation of bone marrow for muscular dystrophies Direct injection of bone marrow stem cells for cardiac regeneration Nuclear Transfer Customized patient specific ES cell Inner Cell Mass Blastocyst G Daley Bone marrow injections for neurodegenerative diseases What are stem cells Units of development and regeneration Stem cell Differentiated cell Liver blood nerve Human development a stem cell hierarchy What are stem cells Differentiation Units of development and regeneration Endoderm Why are stem cells unique Mesoderm 1 They are unspecialized 2 The can produce more stem cells Liver Gut Pancreas Blood Muscle Bone Nervous system Skin 3 They can produce specialized cells Ectoderm Embryonic stem cells Developmental potential Differentiation Developmental hierarchies the hematopoietic system Developmental potential Embryonic versus adult Thymus T cells Isolated from early embryos Can expand indefinitely in culture Can give rise to all cell types NK cells B cells Neutrophil HSC Macrophage Eosinophil Isolated from adult human tissue Can not be expanded in culture Can only give rise to same tissue Erythrocyte Megakaryocyte Mast cell NT to create patient specific Reproductive cloningES cells Nuclear transfer oocyte Donor cell WHY ORGANISM CLONING MIGHT NOT WORK 1 TECHNICAL REASONS 2 GENES OR CHROMOSOMES ARE LOST OR CHANGED IN DEVELOPMENT Nuclear Transfer Customized patient specific ES cell Inner Cell Mass Blastocyst G Daley IN HUMAN FEMALES ONE X INACTIVATED IN DEVELOPMENT DNA IS MODIFIED DURING DEVELOPMENT CH 3 5 methylcytosine 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 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 Cancer as a stem cell disease Low clonogenic ability of tumors in vitro Most tumors are morphologically heterogeneous Nuclear Transfer Customized patient specific ES cell Inner Cell Mass G Daley Blastocyst 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


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MIT 7 03 - Stem Cells and Cancer

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