Amniotic membrane reduces bile duct ligation-induced liver fibrosis

Recently, stem/progenitor cell transplantation has been proposed as potential treatment for chronic liver disorders as an alternative to organ/hepatocyte transplantation. In this study, based on the fact that amniotic membrane (AM) has long been applied in clinic due to its anti-inflammatory and anti-scarring properties and that AM-derived cells display multipotent differentiation potential and immunomodulatory features, we investigated the potential application of human AM as an innovative therapeutic approach. We evaluated the effects of hAM on biliary-type liver fibrosis induced in rats through bile duct ligation (BDL). A fragment of hAM was applied onto the liver surface after BDL and the rats were euthanised after 2, 4 and 6 weeks. The severity of liver fibrosis was assessed both semi-quantitatively by the Knodell scoring system and quantitatively, by digital image analysis, evaluating liver areas occupied by the ductular reaction (CK 19-positive cells), activated myofibroblasts (alpha-SMA-positive cells) and collagen deposition (Masson's staining). hAM-treated rats displayed significantly lower liver fibrosis with respect to control rats. Indeed, in contrast with BDL rats which showed a progression of fibrosis to cirrhosis from week 4 to week 6, fibrosis in BDL+hAM rats was confined at the portal/periportal area, with collagen deposition at about 50% of levels observed in control rats. Concomitantly, AM application slowed progression of the ductular reaction and significantly reduced the area occupied by myofibroblasts. These findings suggest that human AM patching might counteract fibrosis progression in BDL-injured livers and could represent a new strategy to limit hepatic damage associated with fibrotic degeneration