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Gene therapy using SDF-1 and GM-CSF for hindlimb ischemia in mice

Grant number: 15/05250-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2015
Effective date (End): June 30, 2016
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Sang Won Han
Grantee:Gabriel Leonel Marasco
Home Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Peripheral arterial diseases (PAD) has incidence of 10% and this incidence reaches 20% in old people. The main cause of PAD is atherosclerosis, which with the decreasing of blood supply in peripheral tissues will cause local pain leading to risks of amputation. For the blood flow reach normal levels again, leading to better functionality and better life quality, it is necessary to have new vessels formation by expressing angiogenic factors. The stromal derived factor (SDF-1) has shown to be very effective in the induction of angiogenesis, because mobilize endothelial progenitor cells (EPCs) to ischemic regions, promote partial incorporation of these cells in new vessels and induct the expression of VEGF. The granulocyte macrophage colony stimulating factor (GM-CSF) not only has showed to be effective in the induction of angiogenesis but also in arteriogenesis, because mobilize EPCs from bone marrow to peripheral circulation and it is capable of inhibit the apoptosis of monocytes that will participate of tissue remodeling during ischemia. The results observed until now in pre-clinic studies with SDF-1 and GM-CSF have showed to be very promising, but the same didn't happen with the clinic study, showing that these studies need to be improved. On this project we aim the delivery of this two factor on genic form attempting to get a higher migration of pro-vasculogenic cells preventing or attenuating the progression of PAD.