Scientific reports · 2019
Adoptive Transfer of Bone Marrow-Derived Monocytes Ameliorates Schistosoma mansoni -Induced Liver Fibrosis in Mice.
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de Souza Veruska Cintia Alexandrino, Moura Danielle Maria Nascimento, de Castro Maria Carolina Accioly Brelaz, Bozza Patrícia Torres, de Almeida Paiva Ligia, Fernandes Camila Juliet Barbosa, Leão Renata Lins Carneiro, Lucena Jéssica Paula, de Araujo Roni Evencio, de Melo Silva Alex José, Figueiredo Regina Celia Bressan Queiroz, de Oliveira Sheilla Andrade
Аннотация
Liver diseases are a major health problem worldwide leading to high mortality rates and causing a considerable economic burden in many countries. Cellular therapies as potential treatments for liver diseases have proven beneficial in most of the conditions. In recent years, studies involving therapy with bone marrow cells have been implemented to promote liver regeneration and to reduce hepatic fibrosis, however identifying the cell population present in the bone marrow that is responsible for hepatic improvement after therapy is still necessary. The aim of the present study was the evaluation of the therapeutic efficacy of monocytes obtained from bone marrow in fibrosis resulting from S. mansoni infection in C57BL/6 mice. Monocytes were isolated by immunomagnetic separation and administered to the infected animals. The effects of treatment were evaluated through morphometric, biochemical, immunological and molecular analyzes. Monocyte therapy promoted reduction of liver fibrosis induced by S. mansoni infection, associated with a decrease in production of inflammatory and pro-fibrogenic mediators. In addition, monocyte infusion caused downregulation of factors associated with the M1 activation profile, as well as upregulation of M2reg markers. The findings altogether reinforce the hypothesis that the predominance of M2reg macrophages, producers of immunosuppressive cytokines, may favor the improvement of hepatic fibrosis in a preclinical model, through fibrous tissue remodeling, modulation of the inflammatory response and fibrogenesis.