Transplantation of Human Amniotic Membrane over the Liver Surface Reduces Hepatic Fibrosis in a Cholestatic Model in Young Rats

Abstract

Purpose Biliary atresia precedes liver cirrhosis and liver transplantation. Amniotic membrane (AM) promotes tissue regeneration, inhibits fibrosis, and reduces inflammation. Here, we test amniotic membrane potential as a therapeutic tool against cholestatic liver fibrosis. Methods Three groups of rats were used: sham surgery (SS), bile duct ligature (BDL), and bile duct ligature plus human amniotic membrane (BDL + AM). After surgery, animals were sacrificed at different weeks. Biochemical and histopathological analyses of liver tissue were performed. Collagen was expressed as a percentage of total liver tissue area. qPCR was performed to analyse gene expression levels of transforming growth factor-β1 (Tgfb1) and apelin (Apln). Statistical analysis performed considered p < 0.05 was significant. Results Groups undergoing BDL developed cholestasis. Biochemical markers from BDL + AM group improved compared to BDL group. Ductular reaction, portal fibrosis, and bile plugs were markedly reduced in the BDL + AM group compared to BDL group. Collagen area in BDL + AM group was statistically decreased compared to BDL group. Finally, expression levels of both Apln and Tgfb1 mRNA were statistically downregulated in BDL + AM group versus BDL group. Conclusion AM significantly reduces liver fibrosis in a surgical animal model of cholestasis. Our results suggest that AM may be useful as a therapeutic tool in liver cirrhosis.

Sutureless Transplantation of Amniotic Membrane Using a Visible Light‐Curable Protein Bioadhesive for Ocular Surface Reconstruction

“…In the processes of reepithelization, epithelial cells migrate upon stromal collagen; however, reepithelization is delayed by the production of collagen matrix with living scarring by fibrosis in the absence of a basement membrane [ 57,58 ] Thus, the AM reduces fibrosis by providing a basement membrane on which conjunctiva cells can migrate. [ 59 ] The degree of fibrosis was evaluated by measuring the average blue color‐stained ratio after AMT. As a result, there were no significant differences in the average ratios among the FixLight‐treated (37.65 ± 13.65%), fibrin glue‐treated (36.54 ± 11.34%), and suture‐treated (35.68 ± 8.81%) groups at day 3 post‐surgery (Figure 7b).…”

Exosomes Secreted from Amniotic Membrane Contribute to Its Anti-Fibrotic Activity

“…The current treatments for pulmonary fibrosis mostly are drugs targeting signal transduction pathways involved in fibrosis to prevent the excess deposition of extracellular matrix [ 52 , 53 ]. The potential of AM in treating fibrotic diseases has been studied in animal models [ 16 , 17 , 18 ]. The anti-inflammatory and anti-fibrotic activities of AM have also been demonstrated in vitro [ 21 , 54 ].…”

“…Application of AM tissue directly onto fibrotic liver has been studied in rodent models, and the reduction in liver fibrosis has been reported [ 15 , 16 , 17 , 18 ]. While the application of amniotic membrane to fibrotic organs of human patients is challenging, exosomes from AM tissues may be a more attractive alternative.…”

“…Exploring the benefits of AM in treating fibrotic diseases has become one of the major focuses of anti-fibrosis research. Anti-fibrotic activity of fresh AM has been reported in animal models [ 15 , 16 , 17 , 18 ]. AM contains multiple anti-fibrotic growth factors and cytokines.…”

Amnion-derived hydrogels as a versatile platform for regenerative therapy: from lab to market

“…Fibrosis is a well-recognized hypertrophic pathological characteristic observed during the wound healing process that occurs due to excess secretion of fibroblast cells activated by TGF-β1 ( Garrido et al, 2018 ). TGF-β1 stimulates fibrogenesis by encouraging the synthesis of ECM and the deposition of collagen by resident cells ( Gonçalves et al, 2014 ).…”