Objective
Despite the enormous progress achieved in the development of gene transfer technology over the last 10 years, the widespread application of somatic cell gene therapy for genetic and acquired diseases is still limited by the kinds and numbers of available target cells. That is, the difficulty of isolating and expanding lineage and tissue-specific stem cells is now the single most important limiting factor in gene therapy. Our goal is to obtain such specific stem cells by selecting and expanding in-vitro stem cells of mouse and human origin -- the former being essential for laboratory investigation, the latter for therapeutic application.
Specifically, we propose the following lines of research:
1. The feasiblity of deriving various types of lineage-committed stem cells fro mouse embryonic stem (ES) cells will be investigated.
2. From specific human and mouse tissues and organs, we will isolate stem cells committed to the lymphopoietic, megakaryopoietic, myogenic, lungepithelial, keratinocytic, and neural (mouse only!) lineages.
3. Using appropriate markers and animal models in which to evaluate survival, expansion, and differentiation potential in-vivo, we will assess the possibility of utilising such lineage- committed stem cells as vehicles for somatic gene therapy.
We wish to make it clear that we will not produce and/or utilise human ES cells. Apart from the controversial nature of any such undertaking, we believe that it will never be ethically acceptable. Actually, even the mouse ES cell system will only be used in this project for the production of committed lineage-specific stem cells.
The pivotal technology in the entire project is based on the possibility of conditionally immortalising stem cells of different tissues and organs. For this purpose, we will utilise a temperature sensitive mutant of the SV40 large T antigen, the tsA58 gene, which is known to be able to immortalise myogenic cells and keratinocytes. Modification and exploitation of this potentially revolutionary technology are described in detail in the next sections of the project.
Our partnership includes several high-quality, well-established laboratories and some promising, more recently established laboratories in less well-endowed regions of Europe (e.g. Antonio Bernad's laboratory in Spain). The project will concentrate European efforts in the stem cell field toward the development of the best cell vectors for somatic gene therapy. It will provide training within the European community for young scientists, of a level otherwise only possible in the USA.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- medical and health sciences medical biotechnology cells technologies stem cells
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Coordinator
20132 Milano
Italy
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