Key Benefits:
Acting Director General of the Biomedicine Agency,
Vu la Act No. 2013-715 of 6 August 2013 to amend the Act No. 2011-814 of 7 July 2011 relating to bioethics by authorizing under certain conditions research on embryo and embryonic stem cells;
Vu le Public Health Codearticles L. 2151-5, R. 2141-17 to R. 2141-23, and R. 2151-1 to R. 2151-12;
Considering the Order of the Minister of Social Affairs and Health of June 17, 2014 appointing the Acting Director General of the Biomedicine Agency effective July 4, 2014;
Considering the decision of the Director General of the Agency for Biomedicine of 12 March 2010 authorizing the Institut Pasteur to implement a research protocol on human embryonic stem cells;
In view of the decision of 17 September 2013 setting the application file model for the authorizations referred to in theArticle R. 2151-6 of the Public Health Code ;
Considering the application submitted on March 31, 2014 by the Institut Pasteur for the purpose of obtaining the renewal of its authorization for research protocol on human embryonic stem cells;
Considering the additional information provided by the applicant;
Considering the report of the inspection mission of the Biomedicine Agency dated 19 May 2014;
Considering the expert reports of 10 and 12 May 2014;
Having regard to the advice issued by the Guidance Board of the Biomedicine Agency on June 26, 2014,
Considering that the project of the team of Sylvie Garcia is to develop an animal model (smile) reconstituted with a human hematopoietic system, for example a functional immune system; that it is to reconstitute immuno-deficient (alymphoid) mice from transplants of hematopoietic precursors from human embryonic stem cells (homogeneous and unlimited source of precursors),
Considering that the originality of the project lies in the use of complex immuno-deficient mice, whose immune deficit has been developed by incapacitation of three genes essential to the development of T lymphocytes (Rag-/-c-/-C5-/-), and which express a group of the major human histopoly complex (HCM) replacing the equivalent murine molecules (HADR1 transgenic mice; T functional in thymus is only done if they are "recognized and educated" by thymus cells;
Considering that the team's approach is to determine the conditions for obtaining a hematopoie (production of the various cell types contained in the blood) human in a model of immuno-deficient mice from human embryonic stem cells (CSEH) by initially engaging these cells to a specification in hematopoietic progenitors and in particular to lymphoid lines;
That it is therefore a research protocol in a medical purpose;
Considering that in the state of scientific knowledge it can be carried out without resort to human embryonic stem cells; that the expected result can be obtained by other means, in particular by the exclusive use of other stem cells; that the objective of the application is to obtain in vivo models, requiring all elements to create an integrated physiological system, including a Hisefficiency
Considering that a first authorization was granted to this team in 2006 for a period of four years and was renewed in 2010 for an additional four years; that the initial protocol has encountered several scientific difficulties (necessity of introducing the expression of a human gene - SIRP - in the original hosts in order to make them permissive to a transplant and re-enactment by human precursors) and strategic (change of the initial model of retirement
Considering that the application is part of the continuity of the previous protocol and will continue according to the steps mentioned in the application file for authorization;
- to continue the development conditions, from CSEH, of an effective and representative hematopoiesis of the adult hematopoiesis (and not embryonic or fetal); that few are the teams that have managed to get from human embryonic stem cells of the adult hematopoietic stem cells, without the reason for these failures actually appear
- to obtain in vivo in mice the effective and sustainable reconstruction of a human immune system after transplanting hematopoietic progenitors from CSEH, including the production of functional immune cells (lymphocytes T and B, essential to the response to infectious agents) and possibly of cells of innate immunity (macrophages, dendritic cells); that the team identified recently
- develop an effective immune response, i.e. an HLA identity between transplanted hematopoietic progenitors and transgenic mice thymic cells expressing HLA-2, by selecting HLA-compatible HLA-compatible CSEHs; that this restriction indispensable to the immune response justifies the use of human embryonic stem cells, of which the HLA phenotype is known, rather than
- develop a very original strategy to productively infect the liver of mice by HVB (virus that in principle only infects human hepatocytes), and study of the immune response;
Considering, therefore, that the applicant provides sufficient information on the scientific relevance of the research project on the one hand, and its conditions of implementation under the ethical principles on the other; that it justifies in particular that the project will be carried out in accordance with the ethical principles of research on embryo and human embryonic stem cells and that these cells have been obtained in accordance with the fundamental principles provided for in the Articles 16 to 16-8 of the Civil Code, and with the prior consent of the reproductive couple, and without any payment, in any form, being allocated to them; that the titles, diplomas, experience and scientific work provided in support of the application allow to ensure the skills of the research officer and the members of the research team in this matter;
Considering that premises, materials, equipment, processes and techniques are adapted to the proposed research activity,
Decides:
The Institut Pasteur is authorized to implement, under the conditions described in the application for authorization, the research protocol on human embryonic stem cells with the purpose of establishing man/souris animal models: application to the study of chronic human infections. This research is under the responsibility of Ms. Sylvie Garcia.
This authorization is granted for a period of five years. It may be suspended at any time for a maximum of three months, in the event of a violation of the legislative or regulatory provisions, by the Director General of the Biomedicine Agency. Authorization may also be withdrawn, in accordance with the terms and conditions set out in the provisions of Public Health Code.
Any changes to the elements in the application for authorization must be made available to the Director General of the Biomedicine Agency.
The Assistant Director General for Resources of the Biomedicine Agency is responsible for the execution of this decision, which will be published in the Official Journal of the French Republic.
Done on 11 July 2014.
For the Acting Director General:
The medical and scientific director,
K. Laouabdia-Sellami
