Indução de proliferação hepática utilizando uma plataforma polimérica em camundongos

Abstract

The liver is indispensable for maintaining body homeostasis by acting in the metabolic processes. It is an organ that has developed an important characteristic of regenerating itself. Despite of many studies about on liver regeneration, liver diseases are still causes of death by subsequent failure depending on the lesion degree. Therefore, bioartificial liver systems have been proposed as surrogates for end-stage liver failure. Here, we report a polymeric biological platform that induced sequential proliferation of liver parenchyma inside the scaffold in mice. Porous discs of polyetherpolyurethane were surgically placed on the liver and removed at days 4, 8, 12 and 25 after implantation. No exogenous growth factors or extracellular matrix components were added to the scaffold. This biohybrid device provided a scaffold that was gradually filled with parenchymal and non-parenchymal liver tissue as detected by histological analysis. By days 12 and 25 a liver-like structure filled 2/3 of the scaffold, its organization resembled that of a mature liver, inclusive vascular components. Therefore, hepatocytes and other cells were stained to immunohistochemistry for cell proliferation marker. By Picrosirius staining it was shown that collagen deposition in hepatic tissue into implant was similar to the control liver. MPO activity was higher in the first time evaluated (8 days post-implantation) and NAG activity was higher at day 25 post-implantation. TNF- levels were elevated on days 8 and 12, returning to baseline at 25 days, VEGF levels peaked at day 8 and TGF-1 levels were similar at all-time points evaluated. The serum concentration of total proteins, albumin and AST did not change during the experimental period, only ALT increased initially after implantation, but gradually returned to control levels. The synthetic porous scaffold (without addition of exogenous factors) placed adjacent to the native animal liver exhibits the potential to be exploited to investigate physiological mechanisms of liver regeneration.