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Endothelial Stem and Progenitor Cells: Optimized strategies to regenerate ischemic tissues in peripheral vascular disease

English title Endothelial Stem and Progenitor Cells: Optimized strategies to regenerate ischemic tissues in peripheral vascular disease
Applicant Kalka Christoph
Number 114100
Funding scheme Project funding (Div. I-III)
Research institution Department for BioMedical Research Universität Bern
Institution of higher education University of Berne - BE
Main discipline Cardiovascular Research
Start/End 01.10.2006 - 30.09.2009
Approved amount 262'167.00
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All Disciplines (2)

Discipline
Cardiovascular Research
Clinical Cardiovascular Research

Keywords (5)

endothelial stem and progenitor cell; postnatal neovascularization; peripheral vascular disease; tissue regeneration; cell therapy

Lay Summary (English)

Lead
Lay summary
Background
Peripheral artery disease (PAD) accounts for a sizable portion of annual health-care expenditures. Furthermore, beyond the actual health-care money spent, PAD is a major cause of disability, loss of work and lifestyle limitations. Despite the development of improved medical and surgical therapies and the significant advances in the understanding of the basis of disease pathogenesis, millions of people are continue to live with life-threatening atherosclerotic vascular diseases. Among those, symptomatic peripheral vascular disease carries at least a 30% risk of death within five years and almost 50% within 10 years, primarily due to myocardial infarction (60%) or stroke (12%). Limb loss, while only occurring in a minority of patients, is associated with severe disability and overall poor prognosis.

Working Hypothesis
New cellular-based therapeutic strategies are being developed in response to the shortcomings of available treatments for cardiovascular diseases.
One such area, cell therapy, the use of living cells in the treatment of medical disorders, holds enormous potential as an approach to treat cardiovascular diseases as it provides a unique opportunity to address the underlying pathophysiology. The transplantation of healthy cells and grafting into the diseased tissue can either be used in conjunction with, or as a replacement to, traditional therapies. Based on animal studies, preliminary clinical trials for the treatment of acute limb ischemia have shown promising results. However, there exists no fundamental data which clearly establish the optimal delivery system and the most potent progenitor cell population to use for effective neovascularization and regeneration in critical limb ischemia.

Experimental design
The target of the specific aims of the proposal is to initiate a clinical trial for patients suffering from symptomatic peripheral vascular disease.
First, we explore the optimal source of stem cells with regards to the number achievable. We will then seek to define the angiogenic potency of endothelial stem and precursor cells at different stages of differentiation (CD133+, CD34+ cells and ex-vivo cultured EPC) with in vitro assays, as well as in vivo experiments in animal models of tissue ischemia. In addition, the optimal cell delivery system will be investigated. Third, we will address the issue of impaired progenitor cell function in atherosclerosis by analyzing the cell therapeutic effect of stem and precursor cells isolated from the peripheral blood of patients with symptomatic peripheral vascular disease to define the most potent cell population for successful and persisting therapeutic neovascularization.

Potential impact of the proposed project We anticipate that the results of these experiments will yield new insights regarding both the fundamental biology as well as therapeutic applications of stem and progenitor cells for postnatal neovascularization. If we are successful, these results will resolve critical issues concerning the efficacy and reliability of cell therapy sufficiently to permit efficient and long-lasting translation of promising animal studies into clinical studies.
Direct link to Lay Summary Last update: 21.02.2013

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