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Stem cell therapies – and the future of medicine Peter Rathjen Mammalian embryogenesis Embryonic Stem (ES) Cells ICM (stem cells) Blastocyst Isolate ICM Culture in vitro (+LIF) ES Cells Properties of ES cells in vitro ES Cells Differentiate Blastocyst Immortal Pluripotent Differentiated Cells Unlimited numbers, of any kind of cell Cell Therapies “An unlimited supply of any kind of cell with any genetic modification” Cell replacement: Parkinson’s disease (nerves) Stroke (nerves) Heart disease (muscle) Diabetes (pancreas) Immune system (blood) Blindness (Retinal cells) Gene therapies: Thalassemias (blood) Dystrophies (muscle) Cell Therapy with ES cells: how it will work Somatic cell biopsy Patient Nucleus Enucleated oocyte + + Enucleated ES cell Transplant into Differentiation patient Cell product Master cell bank Donor embryo ES cell Human neurons from human ES cells Human ES Cells Differentiation ∂ ∂ Neurons Cell Therapy with ES cells: how it will work Somatic cell biopsy Patient Nucleus Enucleated oocyte + + Enucleated ES cell Transplant into Differentiation patient Cell product Master cell bank Donor embryo ES cell ES cell-derived neurons in vitro Neurons identified by expression of the neural marker, tubulin- III Origin of Ectodermal Lineages in Mammals PLURIPOTENT 4.5 d.p.c. ICM 5.5 d.p.c. primitive ectoderm 6.5 d.p.c. Endoderm ectoderm surface ectoderm +BMP4 neural plate neurectoderm neural tube PNS CNS skin hair ECTODERMAL Mesoderm Cell Therapy with ES cells: how it will work Somatic cell biopsy Patient Nucleus Enucleated oocyte + + Enucleated ES cell Transplant into Differentiation patient Cell product Master cell bank Donor embryo ES cell Integration of ES cell-derived neural precursors in the adult brain ES cell derived cells in the rat striatum, 16 weeks after injection Correction of disease models Drug induced Parkinsonian model (neural precursors/neurons) Spinal cord lesions (neural precursors) Insulin deficiency (insulin producing cells) *Immune deficiency (bone marrow/gene correction) *genetically modified stem cells Cell Therapy with ES cells: how it will work Somatic cell biopsy Patient Nucleus Enucleated oocyte + + Enucleated ES cell Transplant into Differentiation patient Cell product Master cell bank Donor embryo ES cell Animal Cloning Oocyte donor (Scot. Blackface) Enucleation Animal Cloning Nucleus donor (Finn Dorset) Oocyte donor (Scot. Blackface) Enucleation Insert Mammary Gland Nucleus Surrogate Mother Surrogate “mother” (Scot. Blackface) Natural Birth CLONED ANIMAL SCNT/Therapeutic Cloning: Overcoming Rejection Oocyte donor Enucleation Somatic cell biopsy Nucleus + Somatic +Cell Biopsy Enucleated ES cell ES cell Cell Dedifferentiation: Overcoming Rejection Oct4 Sox2 c-myc KLF4 Fibroblast Inject into mouse blastocyst ‘pluripotent’ cell Inject under mouse skin Contribution to all germ layers Cell Therapy with ES cells: how it will work Somatic cell biopsy Somatic cell biopsy Nucleus Enucleated oocyte Enucleated oocyte Nucleus + + + + Enucleated Enucleated ES cell ES cell Transplant into Differentiation patient Cell product Master cell bank ES cell © Copyright The University of Melbourne 2006
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