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MOUSE LIMB ISCHEMIA GENE THERAPY WITH GM-CSF AND M-CSF GENES

Grant number: 15/13640-3
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2015
Effective date (End): September 30, 2017
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Sang Won Han
Grantee:Bárbara Sampaio Dias Martins Mansano
Home Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Peripheral arterial disease (PAD) is caused by atherosclerosis, which leads to narrowing or occlusion of the vessels that supply blood to the extremities of the body and, in an advanced stage, may present a chronic critical limb ischemia (CLI). CLI patients suffer from chronic severe pain, non-healing ulcers, and often amputation of the affected limbs due to lack of therapeutic options. The formation and remodeling of vessels to improve ischemic tissues depend mainly on the type of macrophages present in the ischemic region. We and other groups have shown that GM-CSF or M-CSF can promote these processes by mobilizing macrophages and hematopoietic stem cells. Although the recovery of ischemic limbs was good for one month follow-up, recovery was not complete in these studies. In hematopoietic hierarchy to form monocytes and macrophages, M-CSF and GM-CSF participate in different stages. While GM-CSF has a broader action, including the maintenance and the mobilization of hematopoietic stem cells and the formation of granulocytes and monocytes, M-CSF is more specific for macrophages formation. As in the physiological process, these two factors work in sync to hematopoiesis, including in pathological conditions, we speculate that the action of these two factors at different times are essential for the treatment of ischemia, a work has not yet seen in the literature. This speculation is the main objective of this project.