The potential of human amniotic membrane transplantation to treat liver fibrosis induced in bile duct ligation rat model

• Grant number: 11/11879-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2012
• End date: May 31, 2014
• 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

Abstract

Liver fibrosis and its progression to the advanced stage, know as cirrhosis are diseases difficult to be treated and often associated with severe morbidity and significant mortality. Currently, liver transplantation remains the only effective treatment, which still presents several limitations of it own. The amniotic membrane (AM), the inner part of the fetal membranes, which are discarded at birth with placenta, may represent an alternative for the repair of liver fibrosis due to its anti-inflammatory, anti-fibrotic, and wound healing properties, as well as for the multipotent differentiation ability and immunomodulatory features of AM-derived cells. Recently, we have demonstrated that placenta-derived cells reduce lung fibrosis in bleomycin-treated mice, and that AM patches reduce post-ischemic cardiac injury in rats. In this context, the purpose of this study is to evaluate the potential of allogeneic transplantation of human amniotic membrane to treat liver fibrosis induced in rats through an experimental model of bile duct ligation (BDL). After 2 weeks of the procedure of the bile duct ligation a fragment of human AM will be applied onto the liver surface and the effects on the fibrotic process will be assessed at different times points in comparison with fibrosis progression in control rats. Two and 4 weeks after AM application, animals of each group will be euthanaised to obtain liver samples, which will be submitted to histological, immunohistochemical 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, and activated myofibroblasts. The regulatory factors of the fibrogenic process, such as TGF-beta and inflammatory (IL-6) and anti-inflamatory cytokines expression (IL-10) will be evaluated by immunohistochemistry and ELISA, respectively. (AU)