Antifibrotic Effects of Human Amniotic Membrane Transplantation in Established Biliary Fibrosis Induced in Rats

Abstract

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 known as cirrhosis, resulting in the need to resort to liver transplantation. Amniotic membrane (AM) has emerged as an innovative therapeutic approach for chronic liver diseases due to its anti-inflammatory, antiscarring, and wound-healing effects. We have recently shown that AM can be used as a patch on the liver surface at the same time of fibrosis induction, resulting in significantly reduced progression and severity of biliary fibrosis. Here we investigated the effects of human AM on the established rat model of liver fibrosis, induced by the bile duct ligation (BDL). We also explored the effect of AM on the expression of transforming growth factor-1 (TGF-1), the main profibrogenic factor in hepatic fibrosis, and the proinflammatory cytokines, tumor necrosis factor- (TNF-), interleukin-6 (IL-6), and anti-inflammatory cytokine IL-10. Two weeks after BDL, the liver was covered with a fragment of AM or left untreated. Six weeks later, the fibrosis was first assessed by the semiquantitative Knodell and the METAVIR scoring systems and, thereafter, by CellProfiler digital image analysis to quantify the area occupied by collagen deposition, ductular reactions (DRs), activated myofibroblasts, and TGF-1. The hepatic cytokines were determined by ELISA. AM-treated rats showed a significantly lower score compared to the control BDL rats (2.50.9 vs. 3.50.3, respectively; p0.05). The collagen deposition, DRs, number of activated myofibroblasts, and TGF-1 were all reduced to about 50% of levels observed in untreated BDL rats. These findings suggest that AM, when applied as a patch onto the liver surface, is useful for treating well-established cholestatic fibrosis, and the mechanism was partly by means of downregulating the profibrotic factor TGF-1 and IL-6.

Antifibrotic effects of total or partial application of amniotic membrane in hepatic fibrosis

“…This hypothesis is supported by studies about hepatic fi brosis and its reversibility (Bataller and Brenner 2005, Kisseleva et al 2012, Sun and Kisseleva 2015, which have demonstrated that the mechanism of liver fi brosis regression is characterized fi rst by the decreased inflammatory and fibrogenic cytokine levels, increased collagenase activity, that degrade eCm, and then the disappearance of myofibroblasts. Consistent with these studies, Sant'Anna et al (2016) showed that the livers treated with Am had a 62% reduction in the main profibrotic cytokine, TGF-β1, when compared to the untreated group Bdl. Indeed, manuelpillai et al (2010) observed the decreased expression of TGF-β1 coupled with an induction of collagen-degrading metalloproteinases, and a reduction of their tissue inhibitors of metalloproteinases, thus, reducing the progression of fi brosis to advanced stages.…”

Management of a chronic radiation necrosis wound with lyopreserved placental membrane containing viable cells

“…The benefits of placental membranes, amnion, and chorion, for the management of burns and chronic wounds, have been extensively outlined in the literature . Fresh placental membrane is inherently anti‐inflammatory, antimicrobial, and antifibrotic . When used as a wound cover, placental membranes maintain a moist environment in the wound, reduce pain, and support angiogenesis, granulation of the wound bed, and wound epithelialization .…”

“…9 Fresh placental membrane is inherently anti-inflammatory, antimicrobial, and antifibrotic. [10][11][12] When used as a wound cover, placental membranes maintain a moist environment in the wound, reduce pain, and support angiogenesis, granulation of the wound bed, and wound epithelialization. 13,14 Development of different tissue preservation methods have led to the commercialization of placental membranes; however, the majority of these preservation methods destroy viable tissue cells.…”

Long-term effects of human amniotic membrane in a rat model of biliary fibrosis

“…The reduction in the amount of TGF-β in the hepatic tissue has been used to explain part of the mechanism of fibrosis reduction observed in other therapies such as administration of curcumin (38), chromium (17), and artemisia herb (39). Indeed, the recent study published by Sant'Anna et al (40) confirmed that AM applied to the liver after 2 weeks of BDL reduces the expression of TGF-β to about 62% compared to untreated controls.…”