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Macrophage modulation and differentiation by microvesicles derived from mesenchymal stromal cells in a model of ischemia and reperfusion

Grant number: 16/03084-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2016
Effective date (End): December 31, 2017
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Niels Olsen Saraiva Câmara
Grantee:Gabriela Sampaio da Silva
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The ischemia and reperfusion injury (IRI) is inevitable in renal transplantation, and the major cause of delayed graft function (DGF), that stills a notorious obstacle to the survival of the transplanted kidney. And the IRI is defined as the set of lesions resulting from deprivation of oxygen and the restoration after ischemia. One of the main aggravating of this insult is the inflammation and infiltration of inflammatory cells, mainly macrophages. These cells are heterogeneous and can be polarized into two subtypes: the classic M1 macrophage, which contributes to inflammation, and the alternative M2 macrophage, which has anti-inflammatory actions involved in post-ischemic renal regeneration. Thus, the macrophage polarization is a key event in the outcome of acute and chronic renal lesions. Therefore, a therapy that may educate and reprogram M1 into M2 macrophages, could convert these cells into allies in the regulation of inflammatory immune response and regeneration of the graft after the IRI. One of the potential reprogramming inducers are the Mesenchymal Stromal Cells (MSCs). Microvesicles (MVs) released by MSCs (MVs-MSCs) are strongly involved in their therapeutic effects, and the replacement of MSCs by MVs may provide greater therapeutic security. Therefore, our hypothesis is that the MVs-MSCs can modulate the IRI damage through the differentiation of M1 macrophages resident in the damaged kidney into an anti-inflammatory and reparative phenotype (M2), controlling the initial inflammatory response and modifying the outcome of injury in a model of IRI. Therefore, our goal is to develop an innovative approach in regulating the inflammatory immune response and regeneration of the graft after the IRI.