Objective
Transplantation of hematopoietic stem cells (HSC) is a life-saving treatment for many serious diseases. Unfortunately, the procedure is often hampered by insufficient numbers of donor stem cells and attempts to expand HSCs ex vivo prior to transplantation have remained unsuccessful. An important alternative, which significantly would reduce the required number of donor cells, is to enhance the engraftment efficiency of the transplanted HSCs. The aim of this project is to identify factors that regulate homing and adhesion of HSCs using an RNA interference based screening approach. The principle of the approach is to use lentiviral short-hairpin RNA (shRNA) libraries targeted to HSCs to screen for modifiers of cell adhesion. Adhesive interactions with extracellular matrix and surrounding cells, the so-called niche, are essential for HSC biology. Mesenchymal stroma cells (MSCs) will be used as a model for the adhesive interactions in the hematopoietic niche. When seeded on a layer of MSCs, the vast majority of human HSCs remain adherent to the MSCs. These highly adhesive properties of HSCs constitute a baseline for functional selection of shRNAs interfering with adhesion. Large numbers of HSCs will be targeted with pooled shRNA libraries and candidate shRNAs will be retrieved by functional selection of cells with reduced adhesive properties. The method has been standardized using shRNAs targeting the known mediator of cell adhesion, CD29 (β1 integrin). Knock down of CD29 in HSCs dramatically decreased their adhesion to MSCs. Candidate genes from the screens will be characterized for their role in homing and engraftment of HSCs by assays in vitro as well as in vivo through the ability to repopulate bone marrow of immundeficient NOD/SCID mice. Understanding the basic mechanisms that regulate homing and adhesion of HSCs to their niche is essential in order to develop strategies that may enhance the engraftment process in clinical settings.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences cell biology
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics RNA
- medical and health sciences clinical medicine transplantation
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2009-IEF
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
22100 LUND
Sweden
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.