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Exercise as a tool to enhance the efficacy of mesenchymal cell therapy in a model of peripheral arterial disease

Grant number: 11/18197-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): February 01, 2012
Effective date (End): January 31, 2014
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Sang Won Han
Grantee:Bruno Tesini Roseguini
Home Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Peripheral artery disease (PAD) is a common manifestation of atherosclerosis that affects a considerable portion of the elderly population. Despite of the increasing prevalence and the impact of the disease in the quality of life of the patients, the available treatment options have low cost-effectiveness and are not accessible to the majority of the patients. Mesenchymal stem cell therapy seems to be a promising alternative to promote the functional recovery of individuals with PAD. However, several studies have shown that only a minor fraction of cells transplanted in the affected lower limbs survives, which diminishes considerably the therapeutic potential of this strategy. The major goal of this proposal is to test the hypothesis that a single bout of exercise performed prior to mesenchymal cell administration improves survival and engraftment of these cells in the ischemic tissue and consequently, improves the efficacy of this therapy. Specifically, we hypothesize a single bout of exercise leads to increased expression in skeletal muscle of chemokines and cytokines involved in the attraction and survival of stem cells, such as SDF-1 and its receptor CXCR4. Because of that, exercise should increase the presence of mesenchymal cells in the muscles after the transplant and ultimately, amplify the improvement in functional indexes and vascular density in the lower limbs. Since exercise is non-invasive, accessible and easily applicable, the results of this project could have important implications for the clinical use of mesenchymal stem cell therapy.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ROSEGUINI, BRUNO T.; SILVA, LEONARDO M.; POLOTOW, TATIANA G.; BARROS, MARCELO P.; SOUCCAR, CADEN; HAN, SANG W. Effects of N-acetylcysteine on skeletal muscle structure and function in a mouse model of peripheral arterial insufficiency. JOURNAL OF VASCULAR SURGERY, v. 61, n. 3, p. 777-786, MAR 2015. Web of Science Citations: 7.
SHELDON, RYAN D.; ROSEGUINI, BRUNO T.; LAUGHLIN, M. HAROLD; NEWCOMER, SEAN C. New insights into the physiologic basis for intermittent pneumatic limb compression as a therapeutic strategy for peripheral artery disease. JOURNAL OF VASCULAR SURGERY, v. 58, n. 6, p. 1688-1696, DEC 2013. Web of Science Citations: 10.

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