INSERM (France)
The French Bioethics Law
Since 2004, 25 research groups obtained the authorizations from the Ministry of Health to import hESC lines, to derive new hESC lines from supernumerary embryos, and to develop research projects with hESCs. According to the French Bioethics Law, research projects should:
- Lead to therapeutic progress for serious or incurable diseases and:
- The objectives should not be achievable by other methods of comparable effectiveness
in the current state of knowledge.
The Biomedicine Agency supervises the research to ensure that it strictly conforms to legal regulations. The Bioethics Law prohibits activities including human cloning (both therapeutic and reproductive) and the creation of IVF embryos for research purposes. The Biotethics Law passed in 2004 should be revised in 2010.
INSERM laboratories and platforms involved in hESC and iPS cell research.
I-Stem, Evry.
I-Stem research activity is dedicated to hESC/iPS cell-based cell therapy of monogenic diseases, including Huntington’s disease, Steinert’s disease, Duchenne muscular dystrophy, and Clouston’s disease. I-Stem benefits from a strong support from AFM (Association Française contre les Myopathies). Current research activities include:
- The derivation of iPS cell lines from somatic cells harboring relevant mutations and the subsequent development of protocols for their controlled differentiation into relevant cell types;
- The development of in vitro models of human monogenic diseases based on mutant hESC and iPS cell lines to identify biomarkers and potential therapeutic targets.
http://http://www.istem.eu/ewb_pages/e/english.php
Stem cell and cardiogenesis, Genopole, Evry
It investigates the molecular (genetic and epigenetic) and cellular mechanisms controlling the commitment of hESCs to the cardiac lineage, and the evaluation of the therapeutic potential of hESC-derived cardiac progenitors in the treatment of ischemia and other cardiomyopathies. Furthermore, it is searching for pharmacological targets that could relieve the defects in cardiac development in the laminopathies using hESC and iPS cell models.
Stem Cell and Brain Research Institute, Lyon.
Stem Cell and Brain Research Institute SBRI investigates the development, function and repair of neuronal circuits involved in cognition, motor control and biological rhythms and researches the structural foundations of computation in the cortex. It seeks to develop pluripotent stem cell based therapies so as to reverse the effects of brain lesions leading to the motor and cognitive deficits found in neurological disease including Parkinson's. Current research projects include:
- The identification of novel genes involved in hESC self-renewal and early commitment to germ layers;
- The engineering of rhesus ES and iPS cell lines for imaging studies in the living rhesus monkey;
- The study of the capacity of rhesus ES/iPS cell-derived dopaminergic neurons to improve cognitive deficits and sleep disorders in a monkey model of Parkinson’s Disease.
INSERTECH, INSERM U898, Nice.
INSERTECH’s research activity is dedicated to the study of the molecular mechanisms that control epithelial physiopathology. Current projects aim;
- To identify the genes and signalling pathways involved in the normal and pathological embryonic ectodermal commitment and epithelial differentiation,
- To evaluate the potential of hESC and iPS cells in cutaneous and corneal gene and cell therapy,
- To develop cellular models of congenital diseases (ectodermal dysplasia syndromes, epidermolysis bullosa, and Schizophrenia) using the iPS cell technology.
http://http://www.insermtechnion.com
Institute for Research in Biotherapy (IRB), Montpellier.
IRB research activity is dedicated to research and development in the field of regenerative medicine. Current research activities on hESCs include:
- The identification of the intercellular communication web of pluripotent stem cells and their microenvironment by transcriptomal analysis; characterization of the role of this network in the induction and maintenance of pluripotency;
- The derivation of hESC lines from normal embryos and from embryos harboring genetic abnormalities identified by preimplantation genetic diagnosis;
- The study of the molecular and cellular mechanisms controlling the commitment of hESCs to the hepatic lineage; the development of protocols for controlled differentiation of hESCs into functional hepatocytes and the evaluation of their capacity to restore hepatic function in vivo.
http://http://irb.chu-montpellier.fr/en/introduction.html
Institute of Stem Cell Biology and Cancer (ISCBC), IAL Paul Brousse, Villejuif, University Paris Sud 11.
ISCBC investigates the genetic and epigenetic regulation of proliferation and differentiation of stem cells and cancer cells. Research activities on hESC is supported by a Core Facility which aims to explore the therapeutic potential of hESC and iPS cells in hematology, immunology and hepatology. Current research projects include:
- The derivation and characterization of novel hESC lines from normal and PGD embryos;
- The generation of human iPS to create models of human monogenetic diseases, including predisposition to cancer development;
- The identification of genes and signalling pathways involved in normal and pathological mesodermal commitment (hematopoietic, mesenchymal, endothelial);
- The evaluation of the therapeutic potential of hESC/iPS-derived hematopoietic cell lineages, mesenchymal stem cells and endothelial cells in the treatment of hematopoietic malignancies and cancers.
http://http://www.vjf.cnrs.fr/newial
Institut of Genetics and Molecular and Cellular Biology (IGBMC).
The team investigates the mechanisms of pluripotency in ES and EG cells. It has also developed a core facility to derive hESC cells from PGD embryos with the aim of creating a bank of hESC for the study of monogenic pathologies (in collaboration with I-Stem).
http://http://www.igbmc.fr/recherche/Dep_BCD/Eq_SVivi/index_uk.html
Recent achievements
- A recurrent genomic instability, corresponding to an amplification of 2.5-4.6 Mb at 20q11.21 and encompassing approximately 23 genes, was recently identified in four independent hESC lines. This amplification, which has been associated with oncogenic transformation, may provide a selective advantage to hES cells in culture (Lefort et al., Nature Biotech. 2008, 26:1364-6).
- An improved protocol combining substrates, media and cytokines to differentiate hESC into cells with characteristics of the striatal GABAergic medium-spiny neurons has been developped and tested in the mouse (Aubry et al., Proc. Natl. Acad. Sci. USA, 2008, 105:16707-12)
- A number of novel pluripotency-associated genes have been identified, sheding light on the mechanisms of STAT3 and Nanog-dependent control of pluripotency (Bourillot et al., Stem Cells, 2009, in press).
- Isolation and characterization of a hESC-derived multipotent ectodermal cell line (Aberdam et al. Stem cells, 2009, in press).
- Embryonic stem cells as a cellular model of ectodermal development in human p63-related ectodermal dysplasia syndromes (Rostagno et al. J. Inv. Dermatol., 2009, in press).
- Three-dimensional epithelial tissues generated from human embryonic stem cells (Hewitt et al. Tissue engineering, 2009, in press).
- Twenty-one hESC lines have been established including three hESC lines from normal supernumerary embryos, one hESC line from an embryo with aneuploidy (trisomy 1, monosomy 21), and 17 hESC lines from PGD embryos harboring mutations.
