PROGENITOR · Role of progenitor cells in biology and treatment of atherosclerosis
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-02-01 → 2009-01-31
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- IRG
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Results in brief
Final Activity Report Summary - PROGENITOR (Role of Progenitor Cells in biology and treatment of atherosclerosis)
This study identifies a unique progenitor (precursor) cell in the bone marrow of rodents which we have since also isolated from human subjects. The cell has the capacity for unlimited self-renewal and has several characteristics that mark it as a stem cell. It can change into a smooth muscle cell which is the major cell constituent of blood vessels throughout the body. Therefore in the adult this cell is likely to be very important in terms of the biology of the vascular system (blood vessels). We have identified in this study that this smooth muscle stem cell comes out of the marrow and into the bloodstream when the vessel wall is injured. Indeed this occurs early after injury and subsequently the stem cell participates in the cell changes that occur in the injured vessel. We have shown that if a sufficient number of these cells implant in the injured vessel that narrowing of the artery occurs which may have implications for human patients with vascular disease. The identification of this cell in blood may be a marker for disease extent and activity. Future studies will aim at developing a diagnostic test to detect this unique cell and correlate this assay with vascular disease in humans.
Data: CORDIS, © European Union
Project objective
The concept of atherosclerotic plaque formation as the cause of obstructive vascular disease was proposed more than 100 years ago. Our understanding of atherosclerosis is being continually modified to include vessel wall responses from resident endothelial cells, smooth muscle cells, fibroblasts and circulating blood cell responses from macrophages, lymphocytes and platelets.However, a number of experimental/human studies have called into question the origin of traditionally accepted cellular constituents of atherosclerotic plaque, suggesting that circulating, bone marrow or extravascular sources of precursor cells may be crucially important in reconstituting/remodelling endothelial and vascular smooth muscle elements within the diseased vessel wall.Recently our group isolated and characterized a putative common progenitor cell which possesses multiple angioblastic and myeloid markers. We have shown that committed endothelial and smooth progenitor cells (EPC and SPC) can be differentiated from vascular progenitor cells (VPC) in vitro and that these progenitors can be isolated from mice, rats, pigs and humans.VPC exhibit multiple stem-like features, including clonogenic expansion capacity, unlimited self-renewal, expression of high levels of telomerase and vascular reconstitution capacity. Importantly, adult VPC plasticity appears driven not only by traditional vascular growth or differentiation factors but also by cell-cell contact activation. Study of VPC plasticity may therefore allow fundamental new insights into progenitor composition and remodelling of atherosclerotic plaque.Currently nothing is known about the mobilization, lineage differentiation, homing or integration of these cells in experimental models of atherosclerosis. Therefore the overall objective of this proposal will be to determine the biology of VPC in experimental atherosclerosis, and the therapeutic potential of VPC when used to treat obstructive vascular disease and its complications.
Original text from CORDIS.
Participants
- UNIVERSITY COLLEGE CORK · CORKCoordinatorIreland
Links
Data: CORDIS, © European Union