 EARLY EMBRYONIC DEVELOPMENT: FROM GAMETES AND FERTILIZATION TO STEM CELLS
Dora Brites, Histologia e Embriologia, Faculdade de Farmácia, Universidade de Lisboa
New information is emerging that attests to the importance of stem cells in regenerative biology and medicine. This presentation will address general aspects related to reproduction, early human development and stem cells origin and differentiation, to help set the stage for future interventions. Embryo begins with the fusion of an oocyte and a sperm, but a great deal of preparation precedes fertilization. First, both male and female sex cells must pass through a series of changes that converts them into matures gametes. Spermatogenesis occurs in the testis and in each month one dominant follicle in the ovary undergoes ovulation. Capture of the oocyte by the uterine tube and sperm transport in the male and female tracts must occur before the complex set of interactions leading to fertilization. Meanwhile the cilia in the oviduct push the embryo toward the uterus, the first cleavages occur. The cells of the compacted 8-cell embryo divide to produce a 16-cell morula. By 4 days, the embryo becomes a blastocyst, comprising a fluid-filled cavity (the blastocoele) and two types of cells: a surrounding outer superficial layer (the trophoblast) and a small inner group of cells (blastomeres) that is called the inner cell mass and gives rise to the embryo. Just before implantation, the inner cell mass reorganizes into a bilaminar disk, with epiblast on the dorsal surface and the hypoblast on the ventral surface. During the third week after fertilization the epiblast originates the three embryonic germ layers that will generate the embryo. New cellular and molecular techniques make it possible to isolate embryonic stem cells (i.e., unspecialised cells that are capable of dividing and renewing themselves for long periods) and grown on selected embryonic fibroblast monolayer cultures. Under certain conditions they become cells with special functions. Cells derived from the inner cell mass of the blastocyst (not implanted into infertility patients) or from embryonic germ cells (from spontaneously aborted fetuses) give rise to cells of all tissues of the adult body and are called pluripotent. Adult stem cells typically generate the cell types of the tissue in which they reside and are regarded as multipotent. However, several lines of evidence have suggested that these adult stem cells can also transdifferentiate into different cell lineages, a phenomenon known as plasticity. Recent studies showed that transplanted bone marrow cells are able to differentiate into neural cells. Therefore, the pluripotency of embryonic stem cells and the plasticity of adult stem cells, make them potentially useful to regenerate tissues damaged by disease or injury.
CURRICULUM VITÆ
Name: Dora Maria Tuna de Oliveira Brites Place and Date of birth: Cacém, July 2, 1951 Nationality: Portugueese Institutional adress: Centro de Patogénese Molecular, Faculdade de Farmácia de Lisboa Avenida das Forças Armadas, 28, 1600-083 Lisbon Tel: 21 7946450; Fax: 21 7946491; Email: dbrites@ff.ul.p
Main scientific area of research: Mechanisms of cell damage and response to toxic insult
Other scientific areas of interest: Biochemistry, Molecular and cellular biology, Neonatology, Biomedical Sciences, Analytical Chemistry, Histology and Embriology
Academic degrees, fields of study, awarding institutions: · PhD, Biochemistry, Faculdade de Farmácia, University of Lisbon, Lisbon, Portugal, 1988 · Pharmacy degree, Faculdade de Farmácia, University of Lisbon, Lisbon, Portugal, 1976 · Present positions: Senior Investigator (1996) and Assistant Professor (1989), Fac. Farmácia, University of Lisbon
Previous positions: Research Specialist, Faculdade de Farmácia, 1993 Research Specialist, Centro de Metabolismos e Genética (INIC), 1988 Assistant Researcher, Centro de Metabolismos e Genética (INIC), 1980 Chemist-Analyst, Centro de Metabolismos e Genética (INIC), 1976
Prizes Honour-Soc Port Pediatr,1995; Best work -Pediatr Gastroenterol,1996; Best work-Soc Port Gastroenterol,1999 and 2000; Best commun-Eur Soc Paediatr Res,2000; Best work-Assoc Port Estudo do Fígado, 2001; Research Prize-Ministério da Saúde, 2001; Resesarch Prize-Fundação Calouste Gulbenkian,2002.
Principal Investigator of the present projects: · Inflammatory response and signalling between neurones and astrocytes during cell injury by sepsis, hypoxia-ischemia and hyperbilirubinemiResposta inflamatória e sinalização astrócito-neurónio na lesão celular causada por sepsis, hipóxia-isquémia e hiperbilirrubinémia (FCT -POCTI/FCB/39906/2001) · Is bilirubin-induced apoptosis in nerve cells mediated by TNF-R1? (Fundação Calouste Gulbenkian)
Publications · 48 as full papers and 8 as book chapters Three recent and relevant publications1. Silva RFM, Rodrigues CMP, Brites D. Bilirubin-induced apoptosis in cultured rat neural cells is aggravated by chenodeoxycholic acid but prevented by ursodeoxycholic acid. J Hepatol 2001; 34: 402-408. (Editorial: J Hepatol 2001; 34: 467-470). 2. Brito MA, Brondino CD, Moura JJG, Brites D. Effects of bilirubin molecular species on the membrane dynamic properties of human erythrocyte membranes. A spin label electron paramagnetic resonance spectroscopy study. Arch Biochem Biophys 2001; 387: 57-65. 3. Silva RF, Rodrigues CMP, Brites D. Rat cultured neuronal and glial cells respond differently to toxicity of unconjugated bilirubin. Pediatr Res 2002; 51: 535-41. Long Term Culture and In Vitro Differentiation of Adult Testicular Stem CellsMário Sousa, MD, PhDLaboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (msousa@icbas.up.pt) and Department of Genetics, Faculty of Medicine (genetica@med.up.pt); University of Porto, Portugal Introduction: In vitro culture of adult testicular stem cells is a powerful method for the study of factors controlling germ cell development and may have future clinical implications for infertility treatments and gene therapy experiments.Methods: Sertoli cells (50 SC/case) and diploid germ cells (200 DGC/case) were isolated by micromanipulation from enzymatically dissociated testicular biopsies of 15 patients (46,XY; absence of Yq11.2-AZF microdeletions) with conserved spermatogenesis, after informed consent. Cells were cultured in 40 µl drops under oil for 2-3 weeks (32ºC, 5% CO2 in air). Tested culture media (5 cases/culture type) consisted of Vero cell conditioned medium (CM), CM+rFSH (25 U/L) and CM+rFSH+Testosterone (2 µmol/L). Cells were evaluated regarding chromosome constitution (FISH: X/Y/18), DNA replication (BrdU incorporation), apoptosis (caspase-3 activity) and cell junctions (transmission electron microscopy).Results: Meiosis (3% of in vitro meiosis with formation of haploid new round spermatids) and early spermatid maturation (22.7% of flagellum extrusion in round spermatids) were stimulated by rFSH, whereas rFSH+T further stimulated meiosis (6.7%) and had a positive action over all steps of spermiogenesis (53.8% of flagellum extrusion in round spermatids, 48.5% of differentiation into elongating spermatids, and 16.7% of differentiation into elongated spermatids), with full spermatid differentiation needing a mean of 9 (5-16) days of culture. Cell junctions were only partially reestablished between SC and DGC. Germ cell proliferation appeared stimulated by both hormones (4%) during the first 2 days, kept only under rFSH+T (1%) by day 6, and then stopped. Normal meiotic segregation was observed in secondary spermatocytes (96.5%) and spermatids (84-93%), with a near 1:1 sex ratio. Apoptosis of SC and DGC was significantly inhibited by rFSH and especially by rFSH+T, although degeneration of DGC continued at a high rate (70% by day 6). Apoptosis was similarly inhibited during early spermiogenesis (46 vs 87%), but no effects were observed during mid (10 vs 17%) and late (66 vs 70%) spermiogenesis.Conclusions: The present data suggest that long term in vitro coculture of the normal human seminiferous epithelium (SC and DGC) sustain full germ cell differentiation, at a physiological pace. However, more complex media should be evaluated as the rates of stem cell proliferation and meiosis completion were limited by apoptosis of DGC and detachment of spermatids from SC junctions.Acknowledgements: FCT (36363/99, 43462/01, 35231/99, 42812/01, 48376/02; SFRH/BD/811/00, CF6664/01, CB48376/02; UMIB). Short Biography
Mário Sousa got a medical degree in 1995 (ICBAS/HGSA, University of Porto, Portugal) and the Medical Internship degree (MD) in 1998 (HGSA). He has a Master of Sciences degree (MSc) in Animal Reproductive Biology (1990; ICBAS), a doctoral degree (PhD) in Animal Reproductive Biology (1992; ICBAS), a Post-Doctoral degree in Reproductive Physiology (1993-1995; INSERM 351, Clamart, France), and a medical specialization in Laboratorial Reproductive Medicine (1993-1995, American Hospital of Paris, France). Presently, he is an Associated and Aggregated full Professor of Cell Biology at the Institute of Biomedical Sciences Abel Salazar, University of Porto, Director of Research at the Department of Genetics, Faculty of Medicine, University of Porto, and Scientific Consultant at the Centre for Reproductive Genetics Alberto Barros, Porto. He provides to the community several diagnostic tests, including Transmission Electron Microscopical of germ cells and embryos, Karyotyping, PreNatal Diagnosis, and Molecular Biology of genetical diseases. He also works as a Scientific Consultant for Reproductive Medicine and Genetics to Public and Private Hospitals in Portugal and in several other countries. He also collaborates with Veterinary Sciences in Reproductive Physiology, Genetics and Cloning. His major international clinical achievements were the introduction of ICSI in France (1993, Paris), the first description of the causes of fertilization failure after microinjection (1994, Paris, France), the optimisation of the microinjection technique (1995, Paris, France), the first world babies using round spermatids (1994, Paris, France), the first world baby using elongating spermatids (1997, Alicante, Spain), and the first world babies after in situ hypo-osmotic test (1997, Porto, Portugal). His major clinical achievements in Portugal were the first cases of ICSI (microinjection of sperm from the ejaculate; 1994), MESA (microinjection of sperm from the epidydimus; 1996), TESE (microinjection of sperm and spermatids from the testicle; 1996), Assisted Hatching (1997), Electroejaculation (1997), Retrograde Ejaculation (1997), Long-term Embryo Culture (1998), Cytoplasmic and Nuclear Transplantation (1999), In Vitro Maturation of germ cells (1998-2002), Vitrification (2000) and Preimplantation Genetic Diagnosis (1998). His major international basic research achievements were the discovery of a dual calcium oscillatory mechanism in human oocytes and embryos (1995-1997, Paris, France), the first characterization of the DAZ gene copies responsible for human male infertility (2002, Heidelberg, Germany), and the first world in vitro differentiation of spermatids and sperm after culturing adult testicular stem cells (1998-2002, Alicante, Spain and Porto, Portugal). He directs 15 PhD and 2 Post-Doctoral students, and authored 127 international scientific manuscripts.
Mário Sousa Laboratório de Biologia Celular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto Lg. Prof. Abel Salazar 2, 4099-003 Porto, Portugal Tel: 00-351-22-206 22 17; Fax: 00-351-22-206 22 32Email: msousa@icbas.up.ptMobil: 00-351-91-997.44.76 Grafting
dopamine neurons in Parkinson's disease: do stem cells NAME Jia-Yi Li
POSITION TITLE Associate
Professor 1987 - 1990: University
lecturer, Dept. of Anatomy, Luzhou Medical College, Sichuan, China BETA-CELL REPLACEMENT IN TYPE 1 DIABETES: THE PROMISE OF STEM CELLS. Shimon Efrat, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Israel
Type 1 diabetes mellitus is characterized by a progressive loss of pancreatic b cells, leading to insufficient insulin production. Beta-cell replacement is considered the optimal treatment for type 1 diabetes, however, the availability of human organs for transplantation is limited. An effective cell replacement strategy depends on the development of an abundant supply of b cells and their protection from immune destruction. Stem/progenitor cells, which can be expanded in tissue culture and induced to differentiate into multiple cell types, represent an attractive source of cells for generation of cells with beta-cell properties: insulin biosynthesis, storage, and regulated secretion in response to physiological signals. Embryonic stem cells have been shown to spontaneously differentiate into insulin-producing cells at a low frequency, and this capacity could be further enhanced by soluble agents. Progenitor cells from fetal and adult tissues have also been considered as a potential source for differentiation towards the beta-cell phenotype in vivo, or following expression of dominant transcription factors in vitro. We explored whether human fetal liver progenitor cells (FH) could be induced to differentiate into insulin-producing cells following expression of the pancreatic duodenal homeobox 1 (Pdx1) gene. The replication capacity of FH cells was extended by introduction of the gene for the catalytic subunit of human telomerase. The Pdx1 gene was introduced into these cells using a lentivirus vector carrying a neomycin resistance selection gene. Cells expressing Pdx1 activated multiple b-cell genes, produced and stored considerable amounts of insulin, and released insulin in response to physiological concentrations of glucose. The cells restored and maintained euglycemia for prolonged periods of time in hyperglycemic immunodeficient mice. Quantitation of human C-peptide in the mouse serum confirmed that the glycemia was normalized by the transplanted human cells. We conclude that Pdx1 expression induces differentiation of human fetal liver cells into cells with b-cell properties. Treatment of the modified cells with a number of soluble factors further improved cell phenotype and increased the insulin content to about a third of that of normal beta cells. This approach offers the potential of a novel source of cells for transplantation into patients with type 1 diabetes.
Shimon Efrat, Ph.D.PRIVATE
EDUCATION Bar-Ilan University, Ramat-Gan, Israel, B.Sc., Biochemistry 1975 Hebrew University, Jerusalem, Israel, Ph.D., Molecular Biology 1985
POST-GRADUATE TRAINING Cold Spring Harbor Laboratory, New York, Postdoctoral Fellow 1985-88
PROFESSIONAL APPOINTMENTS Assistant Professor, Dept. of Molecular Pharmacology 1989-93 Albert Einstein College of Medicine Associate Professor, Dept. of Molecular Pharmacology 1993-98 Albert Einstein College of Medicine Visiting Associate Professor, Sackler School of Medicine, 1995-1997 Tel Aviv University, Israel Associate Professor, Sackler School of Medicine, 1997-present Tel Aviv University, Israel Professor, Dept. of Molecular Pharmacology 1998-99 Albert Einstein College of Medicine Visiting Professor, Dept. of Molecular Pharmacology 1999-present Albert Einstein College of Medicine
AWARDS AND HONORS Cancer Research Institute Postdoctoral Fellowship 1986-88 Juvenile Diabetes Foundation Research Awards 1989-2001 Jack E. and Dani Sonnenblick Fellow in Diabetes 1991-99 Irma T. Hirschl Career Scientist Award 1995-99 NIH/NIDDK James A. Shannon Director’s Award 1995-97 Israel Science Foundation Research Awards 1995-2004 Juvenile Diabetes Foundation International Mary Jane Kugel Award 1997 NIH/NIDDK Grant Awards 1997-2002
M. Punzel University of Düsseldorf, Germany
Identification and characterization of perinatal stem cells from the umbilical cord Stem cells from the umbilical cord have become a promising source for allogeneic transplantations. Since the cell number appears to be of outmost importance for engraftment and survival in the clinical setting, our work has been focusing on the identification, isolation and expansion of stem cells from this source. We have developed an assay system that allows a retrospective functional enumeration of human cells that regenerate multipotent hematopoiesis derived from a single cord blood cell. By means of this in vitro method we were able to distinguish the most primitive stem cells from lineage restricted precursors due to the distinct initial cell division behavior. Thus, this technology will allow the prospective identification and isolation of stem and progenitor cells for further graft manipulations. In addition to the analysis of the hematopoietic stem cell, we have also focused on a adherent cell population that can be isolated from the umbilical cord blood low density fraction. These adherently growing cells are CD45-, GlyA-, CD34-, CD14- and share certain markers (SSEA4, Runx1) with embryonic stem cells. We can expand these cells in vitro for more than 20 passages to large quantities. Using specific stimuli, these unrestricted alloantigen negative cells can be differentiated into distinct types of neural cells in vitro. Further, these cells can be differentiated into bone, cartilage, fat, muscle, endothelial, and hematopoietic cells. Preliminary in vivo data have revealed that in contrast to hematopoietic cells, these unrestricted perinatal cells, survived after injection into the mouse liver. Experiments in other animal models (mouse, sheep) are ongoing to determine the overall differentiation potential of these cells. Although, this has not yet been fully analysed on a clonal level, it appears that these unrestricted somatic stem cells (USSC) in the umbilical cord have a much larger differentiation capacity compared those from the bone marrow. This hypothesis is further supported by the ontogenic age of these cells. Thus, given the experience in the clinical banking of cord blood hematopoietic cells, USSC appear to be excellent candidates for the development of allogeneic regenerative cell therapeutics. By employing standard hematopoietic matching protocols these cord blood derived pluripotent stem cells could deliver a universal donor cell population, even in the combination with hematopoietic cells. This will be employed in the development of a feasible platform technology for cellular therapies.
Michael Punzel, M.D.
Heinrich Heine Universität Duesseldorf
phone: +49-211-81-19443
punzel@itz.uni-duesseldorf.de
Professional Career
1985-1991 Medical School in Leipzig, Germany 1991-1995 Residency in Medicine, Leipzig, Germany 1996-1998 Postdoctoral Fellowship at the Department of Medicine, Division of Hematology, University of Minnesota, Minneapolis, MN (Dr. Catherine Verfaillie, Dr. P. McGlave) 1999-2002 Fellowship in Hematology/Oncology Head of the Stem Cell Research Laboratory University of Heidelberg, Germany (Dr. Anthony Ho) since 2003 Senior Research Scientist and Medical Consultant at the Institute for Transplant Diagnostics and Cellular Therapeutics & German Netcord Cord Blood Bank Medical Center University of Düsseldorf
Scientific expertise:
10 peer-reviewed research reports 8 invited reviews and book chapters
Reviewer for several Hematology Journals
Memberships:
International Society of Experimental Hematology, German-Austrian Society of Hematology/Oncology, German Society of Internal Medicine Human (embryonic) stem cells and their potential in cardiac repair
Christine Mummery, Hubrecht Laboratory, The Netherlands.
Ischemic heart disease is the leading cause of mortality in the western world. Oxygen deprivation and even subsequent reperfusion initiates irreversible cell damage, eventually leading to widespread cell death and loss of function. Strategies to regenerate damaged cardiac tissue by cardiomyocyte transplantation may prevent or limit post-infarction cardiac failure. We are using human embryonic stem (hES) cells to try and derive transplantable human cardiomyocytes, capable of replacing the ventricular cardiomyocytes that have been lost following myocardial infarction. We have developed an experimental procedure through which we can induce hES cells to form ventricular cardiomyocytes with properties of the human fetal heart. These cells beat at 60-80 times per minute and can be frozen and thawed without losing their capacity to beat. Groups of cell beat synchronously demonstrating that they are capable of communicating with each other, as myocytes in a normal heart. More importantly, they are able to form functional junctions de novo with primary heart cells in culture. This is an essential property of the cells if they are to function properly after grafting to a defective heart ie. they have to beat synchronously with the host cardiomyocytes and not cause potentially dangerous arrythmias. The induction of arrythmias for example has been a problem when skeletal muscle stem cells from cardiac patients have been transplanted to their hearts; the patients need drugs to control their heartbeat. Bone marrow stem cells are already at the stage of clinical trials but their major contribution to maintaining post-infarct cardiac function appears to be through vasculogenesis; new vessel formation appears to reduce extensive ischemic damage but there is little evidence, at least from animal experiments that bone marrow stem cells give rise to cardiomyocytes. Ultimately a combination of de novo vasculogenesis, perhaps from bone marrow stem cell transplanation, and replacement of cardiomyocytes, perhaps derived from human ES cells, will result in optimal therapies. However, before this takes place, it will be essential to solve problems of culture expansion and large scale production (~109 cardiomyocytes would be necessary to replace those lost during myocardial infarction in one patient). In addition, clinical grade human ES cell lines produced under GMP (Good Medical Practice) conditions will be needed, and it will be necessary to grow these in culture in the absence of animal products (such as calf serum media supplements). Adult stem cells not only have obvious ethical advantages but also potential clinical advantages as the problem of tissue rejection could be obviated by using stem cells from the patient’s own tissues. There remains at present a question mark on the extent to which they can differentiate to cardiomyocytes; direct comparisons between human adult and embryonic stem cell therapies in animal disease models is essential if the relative value of therapies based on these approaches is to be evaluated rigorously for long term effects on functional recovery. Professor Christine Mummery PhD, Group leader and senior scientist Hubrecht Laboratory Expertise : Developmental biology of the heart and vascular system, growth factors and stem cell biology
Christine Mummery took a first degree in Physics at the University of Nottingham in and a PhD in Biophysics at Guy's Hospital Medical School. She then moved to the Hubrecht Laboratory, an institute for developmental biology, in the Netherlands for a postdoc position studying the differentiation of neuroblastoma cells. In 1981 she introduced mouse embryonal carcinoma cells in to the laboratory and 3 years later human embryonal carcinoma cells. Much of this was done in collaboration with Prof Chris Graham and Drs John Heath and Martin Pera in Oxford, UK. In 1985 she spent a short period at the EMBL in Heidelberg with Dr Colin Stewart, where she learnt to derive mES cell lines. She then introduced mES technology into the Hubrecht Laboratory and spent a number of years studying growth and differentiation of these cells. In November 2000, collaboration with Martin Pera and Alan Trounson in Melbourne was re-initiated and she brought their hES cell lines to the Netherlands at the end of that year. First results on their differentiation to cardiomycoytes was recently published (*); current studies involve transplanting these cardiomyocytes into immunodeficient mice with a cardiac infarction. Her laboratory was closely involved in advising on formulation of the law to derive new lines from embryos (the "Embryowet") in the Netherlands. The law permitting human embryo use for this purpose was implemented in September 2002. She applied for ethical approval to derive new lines under this law in March 2003. Christine Mummery has also (co-)authored several reviews on stem cells in regenerative medicine as well as an ethical evaluation of their use(**). In April 2002, she was appointed as professor of developmental biology of the heart at the University of Utrecht Medical School.
Relevant publications (of 110 in refereed journals or book chapters) : van Eijk, M.J.T., Mandelbaum, J, Salat-Baroux, J., Belaisch-Allart, J., Plachot, M., Junca, A.M., Mummery, C.L. Expression of leukemia inhibitory factor receptor subunits LIFRβ and gp130 in human oocytes and preimplantation embryos. Mol. Hum. Reprod. 2:355-360, 1996. Goumans, M-J., Ward-van Oostwaard, D., Wianny, F., Savatier, P., Zwijsen, A., Mummery, C.L. Mouse embryonic stem cells with aberrant transforming growth factor b signalling exhibit impaired differentiation in vitro and in vivo. Differentiation 63:101-113, 1998. Thorsteinsdottir, S., Roelen, B.A.J., Goumans, M-J., Ward-van Oostwaard, D., Gaspar, A., Mummery,C.L. Expression of the a6A integrin splice variant in developing mouse embryonic stem cell aggregates and correlation with cardiac muscle differentiation. Differentiation 64: 173-184, 1999. Goumans, M-J., Zwijsen, A., van Rooijen, M.A., Huylebroeck, D., Roelen, B.A.J., Mummery, C.L. Transforming growth factor b signalling in extraembryonic mesoderm is required for yolk sac vasculogenesis in mice. Development 126: 3473-3483, 1999. Mummery, C.L. D.Ward, CE. Van den Brink, SD Bird, PA. Doevendans, T.Opthof, A. Brutel de la Riviere, L. Tertoolen, M. van der Heyden, M. Pera. Cardiomyocyte differentiation of mouse and human embryonic stem cells. J.Anat.2002; 200:233-242. * Mummery, C.L. D.Ward-van Oostwaard, PA. Doevendans, R.Spijker, S. Van den Brink, R. Hassink, M. van der Heyden, T.Opthof, M. Pera, A. Brutel de la Riviere, R.Passier, L. Tertoolen. Differentiation of human embryonic stem cells to cardiomyocytes: the role of co-culture with visceral endoderm-like cells. Circulation 2003, 107:2733-40 Passier, R, Mummery CL The origin and use of embryonic and adult stem cells in differentiation and tissue repair. Cardiovas.Res.2003. 58:324-35. ** de Wert G, Mummery C.L. Human embryonic stem cells : research ethics and policy. Human Reprod.2003. 18: 672-82. Hassink, RJ, Brutel de la Riviere A, Mummery, CL, Doevendans PA. Transplantation of cells for cardiac repair. J.Am.Coll.Cardiol.2003, 41:711-7. Embryonic Stem Cells and
the status of the human embryo
CURRICULUM VITAE De Walter Osswald
Nome completo: Walter Friedrich Alfred Osswald Local e data de nascimento: Porto, 20 de Setembro de 1928 Nacionalidade: Portuguesa Morada institucional: Instituto de Bioética Universidade Católica Portuguesa (Centro Regional do Porto) Rua Diogo Botelho, 1327 4169-005 PORTO Tel. 226196200/216 Fax. 226196291
Graus académicos: Professor catedrático em 1972 (Fac. Medicina do Porto) Professor extraordinário em 1968 (Fac. Medicina do Porto) Assistente convidado em 1959 (Fac. Med. Univ. Frankfurt) Doutoramento em 1958 (Fac. Medicina do Porto) Licenciado em Medicina em 1951 (Fac. Medicina do Porto)
Áreas de estudo: Farmacologia (inv. em sistema adrenérgico e carviovascular) Terapêutica (ensaios clínicos) Bioética (sobretudo ética médica e ética da experimentação)
Cargo actual: Director do Instituto de Bioética da UCP Membro do Conselho Nacional de Ética para as ciências da vida (CNECV)
Cargos anteriores: Director do Instituto de Farmacologia e Terapêutica da Faculdade de medicina do Porto (1972-1993) Presidente do Gabinete de Investigação(desde 1996
Principal área científica de investigação: Mecanismos adrenérgicos, nomeadamente do aparelho cardiovascular (1953-1993) Ética médica, particularmente da experimentação (1993-
Outras áreas científicas de interesse: Filosofia, Direito (nas suas relações com a Bioética) Organização de reuniões científicas internacionais: Dez edições de “Meetings on Adrenergic Mechanisms” (com o apoio do IAC, JNICT, FCT) Dois simpósios satélites de reuniões internacionais de Farmacologia (Melbourne, 1982, Jerusalém 1980) Um Instituto de Estudos Avançados do NATO Scientific Council (Torre Normanna, Sicília, 1984) Duas reuniões organizadas no âmbito do Gabinete de Investigação de Bioética (1997,1999)
Prémios: 3 Prémios Pfizer
Publicações: Osswald, W. – A relação enfermeiro-doente e a humanização dos cuidados de saúde. Cadernos de Bioética, 23: 41-45, 2000 Osswald, W. – Novas tecnologias, novos poderes, nova ética? Acção Médica 54: 7-12, 2000 Osswald, W. – Os direitos dos doentes como desafio da modernidade. Brotéria, 150: 369-375, 2000 Osswald, W. – Novas drogas, velhos problemas. Brotéria, 150:49-66 Osswald, W. – Investigação médica. In Ética em cuidados de saúde (coord. D. Serrão e R. Nunes), Porto Editora, Porto, 1999, pp. 95-108
Osswald, W. – Futuro da Universidade, Universidade do futuro. Boletim da Universidade do porto, 9 (34): 7-15, 1999 Osswald, W. – O processo dos médicos e o Código de Nuremberg: um olhar crítico. À distância de cinquenta anos. Acção Médica, 52: 5-9, 1998 Osswald, W. – L’etica medica nel terzo milenio. Dolentium Hominum, 13: 74-79, 1998 Osswald, W. – Responsabilities towards the future. Dolentium Hominum 13: 163-165 Osswald, W. – The human
genome project as seen from Arrabida.
Eur. J. Genetics Soc., 2: 17-18, 1997
ALBERTO MANUEL BARROS DA SILVA
Regulation of human embryonic stem cell research in EU Member States
Line Matthiessen-Guyader, MD, PhD, European Commission - DG Research Directorate E "Biotechnology, Agriculture and Food" Unit "Strategic and Policy Aspects" SDME 9/08 B - 1049 Brussels Tel.: +32.2.295.28.53 Fax: +32.2.299.18.60 email: line-gertrud.matthiessen-guyader@cec.eu.int
Opinions on the legitimacy of experiments using human embryos for the procurement of stem cells are divided according to the different ethical, philosophical, and religious traditions in which they are rooted. EU Member States have taken very different positions regarding the regulation of human embryonic stem cell research.
Taking into account the situation, as of June 2003, the following distinctions can be made: – Allowing for the procurement of human embryonic stem cells from supernumerary embryos by law under certain conditions: Belgium, Denmark, Finland, Greece, the Netherlands, Sweden and the United Kingdom. – Prohibiting the procurement of human ES cells from supernumerary embryos but allowing by law for the import and use of human embryonic stem cell lines under certain conditions: Germany. The import and use of human ES cell lines is not explicitly prohibited in e.g. Austria and France and authorisation is still being discussed. – Prohibiting the procurement of human ES cells from supernumerary embryos: Austria, France, Ireland and Spain. The legislation in Spain only allows the procurement of human ES cell from non-viable human embryos under certain conditions. – No specific legislation regarding human embryo research or human ES cell research: Italy, Luxembourg and Portugal. – Allowing by law for the creation of human embryos for research purposes: UK and Belgium are for the moment the only Member State, which allows by law for the creation of human embryos either by fertilisation of an egg by a sperm, or by somatic cell nuclear transfer (SCNT, also called therapeutic cloning) for stem cell procurement. The Dutch Embryo Act of 2002 includes a five-year moratorium for the creation of embryos for research purposes including by SCNT. – Prohibiting the creation of human embryos for research purposes and for the procurement of stem cells by law or by ratification of the Convention of the Council of Europe on Human rights and Biomedicine signed in Oviedo on 4 April 1997: Austria, Denmark, Finland, France, Germany, Greece, Ireland, Netherlands, Portugal and Spain. A number of distinct criteria are applied by Member States allowing for the procurement of stem cells from supernumerary embryos, such as: Free and informed consent, no payment for the cession of the embryo, approval of the research by an authority and / or an ethics committee, purpose of the research, scientific merit of the research and no alternative methods to achieve the objectives. New regulations are under discussion in several Member States, including France, Portugal, Spain and Sweden. Line MATTHIESSEN, MD, PhD European Commission - DG Research Directorate E: Biotechnology, Agriculture and Food – Strategic and policy aspects 200 rue de la Loi, SDME 9/08 B - 1049 Bruxelles Tel.: +32.2.295.28.53 Fax: +32.2.299.18.60 Email: line-gertrud.matthiessen-guyader@cec.eu.int
Curriculum Vitae
Dr. Line MATTHIESSEN is Principal Scientific Officer in the European Commission (EC), Directorate-General for Research, Directorate for Biotechnology, Agriculture and Food. She joints the EC in 1992 and holds a position in the Strategic and Policy unit with responsibly for the ethical aspects of biotechnology. Dr. Line Matthiessen –Guyader held the position as principal scientific officer responsible for research in Neurosciences under the EC research programme “ Quality of Life and Management of Living Resources” (1998-2000). She was also scientific officer in the area of Neurosciences, Somatic gene therapy, Animal cell technology and in vitro testing as alternatives to animal experiments, under the EC - Biotechnology programme (1992-1998). Before joining the European Commission she held several positions as assistant physician in Internal Medicine at the University Hospital Odense, Denmark and at the American Hospital, Paris, France as well as positions as assistant physician in Pathology and Neuropathology, Sainte Anne Hospital and Bichat-Claude Bernard, Paris, France. She was trained as a MD at the University of Odense, Denmark and received her PhD in Neuroscience from the University of Paris VI, France in 1993. Curriculum Vitæ
Nome completo Guilherme Freire Falcão de Oliveira Local e data de nascimento Coimbra, 11 de Novembro de 1947 Nacionalidade Portuguesa Morada Institucional Faculdade de Direito da Universidade de Coimbra Telefone 239.859801 Fax 239.823353 E-mail goliv@fd.uc.pt
Graus Académicos• 1996: foi aprovado por unanimidade nas provas para obtenção do título de Agregado do 4º grupo (Ciências Jurídicas) da Faculdade de Direito da Universidade de Coimbra. • 1988: foi aprovado no concurso documental para o provimento de uma vaga de Professor Associado do 4º Grupo (Ciências Jurídicas); tomou posse do respectivo cargo em Setembro do mesmo ano. • 1984: Doutoramento em Direito Civil, tendo sido aprovado com distinção e louvor, por maioria. •1977-78: Curso de pós-graduação em Ciências Jurídicas, com a informação final de Muito Bom; este Curso veio a equivaler a um Curso de Mestrado, na Faculdade de Direito. •1972: licenciatura em Direito com 18 valores, pela Faculdade de Direito da Universidade de Coimbra
Cargo actual•1996: Professor Catedrático da Faculdade de Direito da Universidade de Coimbra. Foi-lhe atribuída, em quase todos os anos lectivos, a regência de aulas teóricas da disciplina de Direito da Família. e de Direito da Família e das Sucessões. • De 1985 a 1987, e de novo desde 1994/5, foi encarregado da disciplina de Direito Civil no curso de Mestrado em Ciências Jurídico-Civilísticas.
Cargos anteriores• 1988: foi aprovado no concurso documental para o provimento de uma vaga de Professor Associado do 4º Grupo (Ciências Jurídicas); tomou posse do respectivo cargo em Setembro do mesmo ano. • 1984: Professor Auxiliar na Faculdade de Direito da Universidade de Coimbra • De 1985 /86 a 1989 /90 regeu também a disciplina de Teoria Geral do Direito Civil. • 1973: Assistente eventual na Faculdade de Direito da Universidade de Coimbra
Outros cargos• É membro fundador e investigador do Centro de Direito Biomédico da Faculdade de Direito da Universidade de Coimbra, tendo sido encarregado, a partir de Janeiro de 1992, da direcção científica das actividades do Centro. • É membro fundador e investigador do Centro de Direito da Família da Faculdade de Direito da Universidade de Coimbra, sendo encarregado da direcção científica das actividades do Centro, desde 1997.
Principal área científica de investigação Direito da Família Outras áreas científicas de interesse Direito da Medicina
Organização de reuniões científicas internacionais• 2001: Intensiv Course of Medical Law (Erasmus/Socrates Programm) da FDUC — Centro de Direito Biomédico. • 1994: Genoma Humano, Faculdade de Direito Universidade de Coimbra • 1992: Genoma Analysis, Faculdade de Direito da Universidade de Coimbra Prémios• 1985: Condecoração “Ordem do Rio Branco” • 1972: Prémio Beleza dos Santos
Publicações• “O sangue e o direito”, Revista de Legislação de Jurisprudência, no prelo. • “Autoregulação profissional dos médicos”, Revista de Legislação de Jurisprudência, 2001. • Curso de Direito da Família, Vol. I: Introdução. Direito Matrimonial, em co-autoria com Prof. Doutor Francisco Manuel Pereira Coelho, Coimbra: Coimbra Editora, 2001 (2.ª edição). • Temas de Direito da Família, Coimbra: Coimbra Editora, 2001 (2.ª edição). • Critério Jurídico da Paternidade, Coimbra: Almedina, 2001 (reimpressão). • Estabelecimento da Filiação, Coimbra: Almedina, 2001 (reimpressão). • “Implicaciones juridicas del genoma I e II ”, Revista de Derecho y Genoma Humano, 1997. • Temas de Direito da Medicina, Coimbra: Coimbra Editora, 1999.
• Mãe
há só · Genome analysis. In “Genome analysis. Legal rules-Practical application”. Workshop under the auspices of the C.E.C.. Centro de Direito Biomédico da Faculdade de Direito da Universidade de Coimbra/Institut of Pharmaceutical and Medical Law of the University of Goettingen. Coimbra, 11-14 de Junho de 1992. The challenges, the interrogations and the Portuguese reality in the beginning of the XXI century Paula Martinho da Silva
Scientific expectations, medical promises, people’s desire, industry expectations, ethical controversy, legal difficulties and lack of consensus – these are the realities that the world faces while discussing on human stem cell research and use.
Scientific expectations brought by the extraordinary development in this area which raise the possibility of major advances in healthcare; Medical hopes brought by research in the areas of tissues repair and replacement, damaged cells, chronic diseases, serious injuries. People’s desire in the treatment and cure of severe diseases and injuries. Industry expectations on the exploitation of therapeutical products on new therapies, pharmaceutical research, technological services. Ethical controversy on clinical research and mainly on embryonic stem cell research raise the discussion on the respect for human dignity, individual autonomy, justice and beneficence, freedom of research and proportionality. The discussion on the status of embryo takes a new emphasis. Legal difficulties raised by the articulation of the different positions regarding the regulation of human embryonic stem cells research. Binded by legal rules, from the UNESCO Declarations on Human Genome to the Convention of the Council of Europe on Human Rights and Biomedicine, Europe faces a real difficulty to get a common position on the funding of stem cell research in a space where there is no consensus between the legislations of the different European countries. From the non existence of specific legislation regarding human embryo research, from allowing the procurement of human embryonic stem cells from supernumerary embryos under certain conditions to prohibiting such procurement, from allowing the creation of human embryos for research purposes to its prohibition the regulation of human embryonic stem cells in the EU space is far from being consensual.
This is a general overview of what the world faces today on this matter. Portugal, not being an exception faces a double difficulty: the decision making on legislation on embryo research, the lack of legislation on human assisted reproduction and the articulation with the fact of the existence of assisted reproductive centers at least for 15 years and the existence of one unknown number of “spare” embryos.
What would be the choices and even most difficult, how to conciliate the ethical and legal choices with the challenges and promises of medical research? Curriculum Vitae
Profissional name: Paula Martinho da Silva Address : Empreendimento das Amoreiras, Torre 2, 16º, 1070-274 Lisboa Telephone: + 351 21 3843300 Fax: + 351 213870265 Email: pmartinho@bap.pt
Academic Degrees: - Law Degree by the Faculty of Law of Lisbon, Lisbon Classic University (1982). -Master on Bioethics by the Faculty of Medecine, Complutense University of Madrid (1994).
Professional Activity - Lawyer
- Appointed by the Portuguese Prime Minister for President of the National Council of Ethics for the Sciences of Life – 2003 – 2007. - Member of the National Council of Ethics for the Sciences of Life since 1991. -Coordinator of the Bioethics Section at the legislation Commission of the Portuguese Bar Association. - Member of the European Group on Ethics in Science and New Technologies of the European Commission under the direction of Noelle Lenoir 1998- 2000. - Member of the scientific committee of the “International Society of Bioethics”. -Former member of direction of the “Association Internationale Droit, Éthique et Science”. - Former member of the advisory board of the “Journal International de Bioéthique”. - Member of the advisory board of the “European Journal of Health Law”. -Member of the editorial committee of the “Cadernos de Bio-ética” (Center for Bioethics Studies).
Pubilshed Books: - “A Procriação Artificial – Aspectos Jurídicos”, Livros de Direito, Moraes Editores, July 1986. - Convenção dos Direitos do Homem e a Biomedicina, Anotada, Cosmos, July 1997.
Published Books on collaboration - “Procréation Artificielle, oú en sont l’Éthique et le Droit ? « , Lacassagne publications, 1989. - “Bioética” (coord. Luís Archer, Jorge Biscais e Walter Osswald), Verbo, 1996. - “Bem da Pessoa e Bem Comum - um desafio à bioética”, Gráfica de Coimbra, 1998. - “Ethik und Wissenschaft in Europa – die gesellschaftliche, rechtliche und philosophische debatte”, (coord. Dietmar Mieth), Alber, 2000. - “Novos Desafios à Bioética” (coord. Luís Archer, Jorge Biscaia, Walter Osswald, Michel Renaud), Porto Editora, 2001. - “Dicionário de Bioética”, Ed. Perpétuo Socorro, 2001. - “Nouvelle Encyclopédie de Bioéthique” (coord. Gilbert Hottois e Jean-Noel Missa), DeBoeck Université, 2001. - “Comissões de Bioética – das bases teóricas à actividade quotidiana”” (coord. Maria do Céu Patrão Neves), Gráfica de Coimbra, 2002. - “Direitos do Homem e Biomedicina” (colaboration), Instituto de Bioética, Universidade Católica Editora, Janeiro 2003.
Published Articles - “O anonimato do dador”, Boletim da Ordem dos Advogados, nº 1/87. - “Procriação artificial - da ética ao direito”, Revista de Ciência Tecnologia e Sociedade, nº 10, 1989. -“Bioética, o Direito e um breve resumo sobre o quadro legislativo português”, Revista do Ministério Público, nº 43, 1990. -“Investigação biomédica em seres humanos”, Ciência, Tecnologia e Sociedade, nº 12, Abril/Junho, 1991. - “O conflito entre liberdade de disposição e a protecção do individuo”, OMNIA,nº 22, Junho,1991. - “Transplantes – e os incapazes?”, Diário de Notícias, 9 Agosto, 1993. - “Em torno da discussão sobre transplantes de órgãos e tecidos”, Brotéria, 137, 1993. - “Les transplantations d’organes dans les pays ibériques : Portugal et Espagne », Journal International de bioéthique, vol. 5, nº 3, 1994. - « Alguns apontamentos sobre a nova lei dos transplantes », Revista da Associação Portuguesa de Clínicas Privadas de hemodiálise, nº 5, 1995. - “Biotecnologias – do fermento de Pasteur ao gene humano”, Lei Magazine, 1995. - “Genes and patents – is the traditional law out of fashion?”, Revista de Derecho y Genoma Humano, nº 3, Julho-Dezembro, 1995. - “O bio-direito é universalizável? Ou somente harmonisável?”, cadernos de Bio-Ética, nº 19, Abril, 1999. - “Mãe de substituição? Porque não?”, jornal Público, 24 Fevereiro, 2001.
Teaching - on several Masters and Post graduation on Bioethics on Lisbon and Oporto Medicine and Law Faculties.
International Conferences - “Transplantes de órgãos em Portugal e Espanha”, on the “Seminar on the Current Problems of Organ Transplantation”, International Institute of Studies in Human Rights, Triestre, September 1993. - “Acess to medically-assisted procreation”, III Symposium of Bioethics of the Council of Europe on “Assisted Reproduction and Human Embryo Protection”, Estrasburgo, December 1996. - “Ethical Management of Biotechologies: The role of the Group on Ethics in Science and New Technologies”, seminar on “Patentability of Biotechnological Inventions: a new start for Europe”, European Commission, October 1998. - “Ethics and Law”, seminar on “Ethik und Wissenschaft in Europa”, Tubingen, June 1999. - “To a supranational integration of the main principles on Human Genome”, Universidade de Deusto, Bilbao, April 2000. - “Perspectivas Jurídicas Portuguesas e Europeias sobre Fertilização Humana Assistida”, II Portuguese-Brasilian Bioethics Meeting, Brasília, 2002.
Stem cell research: political and public debate in the United Kingdom
Juliet Tizzard is Director of Progress Educational Trust and Editor-in-chief of BioNews.org.uk. A graduate of English Literature, Juliet specialises in writing about reproductive and genetic science for different lay audiences. During her time at Progress Educational Trust, she has also studied for a Masters in Medical Ethics and Law, when she focused upon the ethical issues arising from genetic testing.
jtizzard@progress.org.uk
Stem cell research: political and public debate in the United Kingdom
This presentation will report on the regulation of stem cell research and cloning in the United Kingdom. Human embryo research has been subject to statutory regulation since 1990. However, amendments to the legislation needed to be made before embryonic stem cell research for the development of therapies could proceed. UK regulation will be compared with that in other European countries, as well as the United States and others.
The political climate, public attitudes and media coverage of embryo research will be examined. Public, parliamentary and media attitudes towards stem cell research, although always sympathetic, have become more supportive over the past five years. The reasons for this will be examined, focusing upon particular news stories and regulatory developments.
The passage of the Stem Cell Regulations through the UK parliament will be discussed: from reports from learned societies and bioethics organisations, through to parliamentary debates in the House of Commons and House of Lords. The presentation will discuss how supporters of embryonic stem cell research managed to win parliamentary support and, ultimately, approval for the research.
Some insights from the UK experience will be offered. How public attitudes changed; why media coverage became more sympathetic and how political support for ES cell research was secured.
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