Abstract
Peripheral arterial disease affects millions of people every year and compromises the quality of life and shortens the life expectancy of these patients. The non-healing ulcer and strong chronic pain are the main symptoms of this disease in advanced stage that occurs due to tissue hypoperfusion and can lead to amputation of the affected limb and death. In the ischemic limb a constant inflammation occurs due to hypoperfusion and cell death, and monocytes and macrophages are mobilized to remove necrotic cells and to produce growth factors to promote vessel formation and remodeling, and regeneration and tissue repair. Recently, several subpopulations of monocytes and macrophages were discovered with several biological and paradoxical activities that may favor or disfavor the injured ischemic muscle. The proliferation and differentiation of these cells are dependent on the colony stimulating factors (CSFs), but subtypes of monocytes and macrophages recruited by each CSFs and the influence of these macrophages upon pericytes in the ischemic limb are unknown. The importance of understanding the role of CSFs in gene and cell therapies for ischemic diseases comes from our previous experience, where the administration of GM-CSF gene in vivo or ex vivo by means of mesenchymal stem cells in the mouse ischemic limbs led to almost complete recovery of mass and strength of muscles in 30 days. The main focus of this project is to study the quality of populations of monocytes and macrophages recruited by different CSFs in the ischemic skeletal muscles, and to assess whether the restriction of the M1 macrophage population or recruitment of M2 population is beneficial, and to verify if the tissue macrophage profiles can be changed by the local microenvironment. Influence of macrophages upon pericytes under ischemic and normoxica conditions will be investigated. Results of this study will show new gene interference ways to promote vessel formation and remodeling to repair and to regenerate ischemic tissue more efficiently with less fibrosis. (AU)
Scientific publications
(12)
(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)
TENG, YUAN-CHI;
PORFIRIO-SOUSA, ALFREDO LEONARDO;
RIBEIRO, GIULIA MAGRI;
AREND, MARCELA CORSO;
MEIRELLES, LINDOLFO DA SILVA;
CHEN, ELIZABETH SUCHI;
ROSA, DANIELA SANTORO;
HAN, SANG WON.
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DE MELLO, LUCAS RODRIGUES;
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HAN, SANG WON;
PINTO DE OLIVEIRA, CRISTIANO LUIS;
DA SILV, EMERSON RODRIGO A.
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Journal of Physical Chemistry B,
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MARTINS, GRAZIELI OLINDA;
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MARTINEZ JUNIOR, ANDRE MIGUEL;
DE OLIVEIRA TIERA, VERA APARECIDA;
CALMON, MARILIA DE FREITAS;
LEITE VILAMAIOR, PATRICIA SIMONE;
HAN, SANG WON;
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Amphipathic chitosans improve the physicochemical properties of siRNA-chitosan nanoparticles at physiological conditions.
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JUL 15 2019.
Web of Science Citations: 3.
MADRIGAL, JUSTIN L.;
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TANAKA, KIMBERLY;
REZVANI, SABAH N.;
MORGAN, RYAN P.;
REVZIN, ALEXANDER;
HAN, SANG W.;
SILVA, EDUARDO A.
Microfluidic generation of alginate microgels for the controlled delivery of lentivectors.
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NOV 21 2016.
Web of Science Citations: 10.
STILHANO, ROBERTA S.;
MADRIGAL, JUSTIN L.;
WONG, KEVIN;
WILLIAMS, PRISCILLA A.;
MARTIN, PRISCILA K. M.;
YAMAGUCHI, FABIO S. M.;
SAMOTO, VIVIAN Y.;
HAN, SANG W.;
SILVA, EDUARDO A.
Injectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle.
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v. 237,
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SEP 10 2016.
Web of Science Citations: 17.