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Mechanisms of action of fresh and cryopreserved amniotic membrane in the repair of liver fibrosis induced in rats.

Grant number: 16/10827-8
Support Opportunities:Regular Research Grants
Duration: November 01, 2016 - July 31, 2019
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Luciana Barros Sant'Anna
Grantee:Luciana Barros Sant'Anna
Host Institution: Instituto de Pesquisa e Desenvolvimento (IP&D). Universidade do Vale do Paraíba (UNIVAP). São José dos Campos , SP, Brazil
Associated researchers: Emilia Angela Lo Schiavo Arisawa ; Raduan Hage ; Renata de Azevedo Canevari ; Rodolfo de Paula Vieira


Liver fibrosis is characterized by excessive accumulation of extracellular matrix components in the liver parenchyma that distorts the normal architecture and hepatic function. Progressive fibrosis could end in the advanced stage know as cirrhosis, resulting in the need to resort to liver transplantation. Amniotic membrane (AM) has emerged as an innovative therapeutic approach for regenerative medicine, especially for chronic liver diseases for its anti-inflammatory, antiscarring, wound-healing effects, and the presence of stem cells. Previously, we have shown that AM used as a patch onto the liver surface at the same time of fibrosis induction significantly reduces 50% the area occupied by collagen deposition, inhibiting the progression of biliary fibrosis to the advanced stage, cirrhosis. When AM was applied after 2 weeks of fibrosis induction, the main profibrogenic factor, TGF-b1 and IL-6 were all reduced. However, the action mechanisms of these effects were not fully understood. In this context, the purpose of this study is to evaluate the actions mechanisms of fresh AM as a therapeutic approach for hepatic fibrosis induced in rats through an experimental model of bile duct ligation (BDL) and to analyze the cellular viability and structural integrity of cryopreserved AM. After 2 weeks of the BDL a fragment of human AM will be applied onto the whole liver surface or wrapping only a portion of the liver and analysis of effects of that treatment will be performed on the whole liver. Four weeks after AM application animals of each group will be euthanized to obtain liver samples, which will be submitted to histological, immunohistochemical, double immunofluorescence and digital image morphometric analysis for the evaluation of the following parameters: degree/severity of fibrosis, and the area occupied by collagen deposition, ductular reaction, activated myofibroblasts, number of apoptotic myofibroblasts and proliferating hepatocytes. Some samples will be prepared for gene expression analysis of macrophage subtypes M1 and M2 and metalloproteinase associated with the degradation of the collagen matrix (MMP9, MMP12 and MMP13). Another part of the liver will be used to analyze, by flow cytometry, monocyte precursors of those macrophages, pro-inflammatory cytokines and intracellular anti-inflammatory featuring M1 and M2. (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)
MORAES, JESSICA TEREZA GUEDES DE OLIVEIRA; COSTA, MAIRA MAFTOUM; ALVES, PAULA CRISTINA SANTOS; SANT'ANNA, LUCIANA BARROS. Effects of Preservation Methods in the Composition of the Placental and Reflected Regions of the Human Amniotic Membrane. Cells Tissues Organs, v. 210, n. 1, p. 11-pg., . (16/10827-8)
KARINA M. MAMEDE; LUCIANA B. SANTANNA. Antifibrotic effects of total or partial application of amniotic membrane in hepatic fibrosis. Anais da Academia Brasileira de Ciências, v. 91, n. 3, . (16/10827-8)

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