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O▪100 Nuclear transfer for the production of embryonic stem cells
Abstracts - 6th International Symposium on Preimplantation Genetics 2005
somatic cells, while the neighbouring cells that share common ancestry continue along this path and acquire the same fate as mesoderm. After PGC specification, these cells proliferate and migrate into the developing gonads, when they undergo extensive reprogramming of the genome, including re-activation of the inactive X chromosome, erasure of genomic imprints and genome-wide DNA demethylation. Analysis of these mechanisms of reprogramming in the germ cell lineage will add significantly towards elucidating how erasure and re-establishment of novel epigenetic information occurs, which is essential for regulating diverse genome functions.
O 99 Making cardiomyocytes from embryonic and adult stem cells Mummery C Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands Embryonic stem cells (ESC) derived from blastocyst stage embryos are pluripotent and will form derivatives of all three embryonic germ layers. Stem cells derived from post-natal, somatic tissues are intended for tissue repair and maintenance of adult tissues. They are generally more restricted in their developmental potency. Here, the derivation and characterization of heart cells from human ESC will be described in the context of signals known to regulate heart development and physiology in the embryo. Transplantation of these hESC-derived cardiomyocytes in the mouse heart will be described. Results will be considered in the context of state-of-the-art developments in the transplantation of adult stem cells from bone marrow, skeletal muscle and the heart itself into the myocardium. Issues of safety, efficacy and immunorejection will be discussed, and the merits of each cell type for clinical application will be considered.
O 100 Nuclear transfer for the production of embryonic stem cells Trounson A Monash Immunology and Stem Cell Laboratories, STRIP – Building 75, Monash University, Wellington Road, Clayton, Victoria, 3800, Australia Proof of concept showing that embryonic stem cells can be formed after nuclear transfer of somatic cells into enucleated mouse eggs has enabled the analysis of epigenetic/genetic factors in end differentiated somatic cell phenotypes. These studies enable the analysis of the role of genetic alteration and mutation to genomic DNA and the influence of gene silencing and activated gene expression on cancer phenotypes and terminal variants of differentiation. Nuclear transfer has been used to derive human patient specific embryonic stem cells using human and animal oocytes. This raises the possibility of deriving embryonic stem cells from patients with severe diseases for analysis of the progression of disease phenotype and potential screens for drugs that can modify the disease phenotypes. These are powerful research tools.
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O 101 Stem cell therapy: hope or
hype Braude P Department of Women’s Health, Guy’s, King’s and St Thomas’ School of Medicine, King’s College London, UK The use of human embryonic stem cells is being hailed as the next major step in the battle against serious degenerative disorders like diabetes, heart disease and some neurological diseases. Reading promotional material on websites and news reports, conveys the impression that this therapy is now available or imminently so. Derivation of human embryonic stem cell lines has increased dramatically in the past 2 years, despite either total bans in some countries, or partial bans on use of embryos in others. Fortunately some other countries, have been foresighted enough to see the potential in these therapies, and allowed regulated embryo research. There are, however, still major hurdles to be overcome that will require substantial investment and research. The growth of stem cells under pharmaceutical GMP (good manufacturing practice) conditions is yet to be achieved. Surprisingly, even the embryos from which they would be derived are still cultured in the presence of human or animal products. The premature use of cell therapy could put many patients at risk of major viral or prion illness unless appropriate tests and quality systems are put in place. The lessons of the premature application of gene therapy, and the huge disaster of HIV in the haemophiliac population should not be forgotten. Animal experiments need be conducted to further understand destination, integration and risks of neoplasia, but the transfer of human stem cells into animal hosts has also caused substantial ethical disquiet. A logical progressive approach to the development of lines and their rational therapeutic use is required for this promising therapy to be realised. The danger is that the drive to be first, could see it spiral into the realms of quackery.
somatic cells, while the neighbouring cells that share common ancestry continue along this path and acquire the same fate as mesoderm. After PGC specification, these cells proliferate and migrate into the developing gonads, when they undergo extensive reprogramming of the genome, including re-activation of the inactive X chromosome, erasure of genomic imprints and genome-wide DNA demethylation. Analysis of these mechanisms of reprogramming in the germ cell lineage will add significantly towards elucidating how erasure and re-establishment of novel epigenetic information occurs, which is essential for regulating diverse genome functions.
O 99 Making cardiomyocytes from embryonic and adult stem cells Mummery C Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands Embryonic stem cells (ESC) derived from blastocyst stage embryos are pluripotent and will form derivatives of all three embryonic germ layers. Stem cells derived from post-natal, somatic tissues are intended for tissue repair and maintenance of adult tissues. They are generally more restricted in their developmental potency. Here, the derivation and characterization of heart cells from human ESC will be described in the context of signals known to regulate heart development and physiology in the embryo. Transplantation of these hESC-derived cardiomyocytes in the mouse heart will be described. Results will be considered in the context of state-of-the-art developments in the transplantation of adult stem cells from bone marrow, skeletal muscle and the heart itself into the myocardium. Issues of safety, efficacy and immunorejection will be discussed, and the merits of each cell type for clinical application will be considered.
O 100 Nuclear transfer for the production of embryonic stem cells Trounson A Monash Immunology and Stem Cell Laboratories, STRIP – Building 75, Monash University, Wellington Road, Clayton, Victoria, 3800, Australia Proof of concept showing that embryonic stem cells can be formed after nuclear transfer of somatic cells into enucleated mouse eggs has enabled the analysis of epigenetic/genetic factors in end differentiated somatic cell phenotypes. These studies enable the analysis of the role of genetic alteration and mutation to genomic DNA and the influence of gene silencing and activated gene expression on cancer phenotypes and terminal variants of differentiation. Nuclear transfer has been used to derive human patient specific embryonic stem cells using human and animal oocytes. This raises the possibility of deriving embryonic stem cells from patients with severe diseases for analysis of the progression of disease phenotype and potential screens for drugs that can modify the disease phenotypes. These are powerful research tools.
32
O 101 Stem cell therapy: hope or
hype Braude P Department of Women’s Health, Guy’s, King’s and St Thomas’ School of Medicine, King’s College London, UK The use of human embryonic stem cells is being hailed as the next major step in the battle against serious degenerative disorders like diabetes, heart disease and some neurological diseases. Reading promotional material on websites and news reports, conveys the impression that this therapy is now available or imminently so. Derivation of human embryonic stem cell lines has increased dramatically in the past 2 years, despite either total bans in some countries, or partial bans on use of embryos in others. Fortunately some other countries, have been foresighted enough to see the potential in these therapies, and allowed regulated embryo research. There are, however, still major hurdles to be overcome that will require substantial investment and research. The growth of stem cells under pharmaceutical GMP (good manufacturing practice) conditions is yet to be achieved. Surprisingly, even the embryos from which they would be derived are still cultured in the presence of human or animal products. The premature use of cell therapy could put many patients at risk of major viral or prion illness unless appropriate tests and quality systems are put in place. The lessons of the premature application of gene therapy, and the huge disaster of HIV in the haemophiliac population should not be forgotten. Animal experiments need be conducted to further understand destination, integration and risks of neoplasia, but the transfer of human stem cells into animal hosts has also caused substantial ethical disquiet. A logical progressive approach to the development of lines and their rational therapeutic use is required for this promising therapy to be realised. The danger is that the drive to be first, could see it spiral into the realms of quackery.