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Evaluation of regenerative and reparative effect of IL-4 in ischemic muscle through expansion of type m2 resident macrophages

Grant number: 16/04229-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): October 01, 2016
Effective date (End): September 30, 2018
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Sang Won Han
Grantee:Tâmisa Seeko Bandeira Honda
Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:15/20206-8 - Modulation of monocytes, macrophages and pericytes by the colony stimulating factor genes to treat murine limb ischemia, AP.TEM


Chronic critical limb ischemia (CCI) is characterized by a chronic reduction of the arterial diameter due to atherosclerosis, resulting in tissue hypoperfusion and chronic inflammation of members. The high incidence of CCI plus the low treatment success rates makes individuals with CCI targets to amputations, or may lead to death in severe cases. By analyzing the pathophysiology of CCI, it has been observed that ischemia leads to inflammation and tissue injury, and those macrophages present at the site of injury play a role in the removal of dead cells and tissue repair. It is known that M2 type macrophages are originated from circulating monocytes and resident macrophages, and recent studies have shown that type M2 macrophages play a crucial role in angiogenesis, tissue repair and fibrosis. Among the interleukins, IL-4 is the most active in the polarization of macrophages into type M2 and IL-4 is also involved in the expansion of resident macrophages, especially in animals infected with roundworms. Based on the current knowledge in this area, there are two fundamental questions that must be asked: can a highly expressed IL-4 gene in ischemic skeletal muscle promote in vivo expansion of resident M2 type macrophages? In addition, would this expansion of resident macrophages be sufficient to promote regeneration and recovery of ischemic skeletal muscle? The answers provided to these questions should contribute to a better understanding of reparative and regenerative processes of ischemic skeletal muscle, as well as in the development of therapeutic approaches specifically directed to the ischemic tissue in order to minimize side effects caused by systemic use of drugs. (AU)

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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)
MARTINS, LEONARDO; GALLO, CAMILA CONGENTINO; HONDA, TAMISA SEEKO BANDEIRA; ALVES, PATRICIA TERRA; STILHANO, ROBERTA SESSA; ROSA, DANIELA SANTORO; KOH, TIMOTHY JON; HAN, SANG WON. Skeletal muscle healing by M1-like macrophages produced by transient expression of exogenous GM-CSF. STEM CELL RESEARCH & THERAPY, v. 11, n. 1, . (16/04229-0, 11/15417-9, 18/09203-5)

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