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

Abstract

Liver fibrosis is the final common pathway of chronic liver diseases, having cirrhosis as a possible progression, which has liver transplantation as the only effective treatment. Human amniotic membrane represents a potential strategy as a therapy for liver fibrosis, due to its anti-inflammatory, antifibrotic and immunomodulatory properties. The aim of this study was to evaluate amniotic membrane effects as a treatment for hepatic fibrosis induced in rats by bile duct ligation (BDL), verifying alterations between two different forms of amniotic membrane application, around all the lobes of the liver and around only one lobe of the liver. Two weeks after inducing fibrosis, an amniotic membrane fragment was applied to the surface of the liver, covering it either totally or partially. Four weeks later, the animals were euthanized and liver samples were collected. Histopathological and quantitative analyses demonstrated fibrosis severity decrease and an extremely significant reduction in the deposition of collagen in the groups treated with amniotic membrane, particularly when the amniotic membrane was applied in only one liver lobe. It is concluded that the amniotic membrane acted on the repair of liver fibrosis in both modes of application, with the application of the amniotic membrane around only one hepatic lobe being more effective in reducing the severity / extent of fibrosis.

Biological properties and surgical applications of the human amniotic membrane

“…In a rat model of cirrhosis generated by bile duct ligation, the fibrosis process was generated 2 weeks later. Fresh AM was placed on the hepatic surface totally or partially and, 4 weeks later, a decrease in the severity of fibrosis was histologically verified, due to a decrease in the amount of collagen deposits ( Sant'Anna et al, 2011 ; Ricci et al, 2013 ; Mamede and Sant’anna, 2019 ). In post-operative pancreatic fistula after pancreatic resection, cryopreserved AM was applied with the aim of tissue regeneration and preventing fluid leakage at many surgical sites ( Figure 4 ).…”

Placental-Derived Biomaterials and Their Application to Wound Healing: A Review

“…The sheet ECMs possess the properties associated with their tissue of origin [56]. For example, AM sheet scaffolds are thought to promote healing via epithelialization [143][144][145], reduction of inflammation [6,[79][80][81], inhibition of scar tissue formation [85,86], and the ability to act as an antimicrobial agent [82][83][84]. In addition, sheet scaffolds are modified to improve the mechanical properties of the tissue and are available in many configurations, including single layer and multilayer [6], full-thickness, and composite grafts.…”

Amniotic Membrane and Its Derivatives: Novel Therapeutic Modalities in Liver Disorders

“…Taken together, biomedical application of hAM and its derivatives is a developing market and could be used for biomedical research and treatment of liver diseases. Human amniotic epithelial cells (hAECs) murine NASH model increased total levels of anti-fibrotic IFNβ in mice treated with a single dose of hAECs [86] Human Amniotic membrane (hAM) Bile duct ligated Rat Reduced liver fibrosis in a surgical animal model of cholestasis [106] Human Amniotic membrane patch Bile duct ligated Rat application of the amniotic membrane around only one hepatic lobe was being more effective in reducing the liver fibrosis [107] Human Amniotic membrane patch Wistar albino rats Applied amniotic membrane to residual liver adversely affected liver regeneration [108] Human Amniotic membrane patch Bile duct ligated Rats AM patch reduce fibrosis by downregulating the profibrotic factor such as TGF-b1 and IL-6 [109] Human amniotic mesenchymal stromal cells (hAMSCs) Acetaminophen (APAP) induced liver injury mice hAMSCs suppressed M1 polarization and promoted M2 polarization of Kupffer cells through regulating autophagy [110] amniotic epithelial cells (AECs) Rat and human Amniotic epithelial cells (AECs) AECs can respond to proangiogenic signals in vitro and differentiate into HSECs in vivo [111] Human amniotic membrane-derived mesenchymal stem cells (hAMCs) Immunocompetent CCL4 treated mice suppressed activation of hepatic stellate cells, decreased hepatocyte apoptosis and promoted liver regeneration [112] Mice amniotic-fluid-derived stem cells (mAFSCs) CCL 4 treated mice Reduced fibrosis by mAFSCs injection [113] human amniotic membrane-derived mesenchymal stromal (hAMSCs) and epithelial stem cells (hAECs) CCL 4 -cirrhotic rats Rats that received amnion derived stem cells had markedly reduced hepatic inflammation and oxidative stress/improved liver function in rats receiving hAMSCs [114] Human amniotic membrane patch Bile duct ligated Rats AM patch could attenuate the severity of biliary fibrosis for longer periods [115] Human amniotic epithelial cells (hAECs) Bile duct ligated Rats Reduced fibroblast numbers/reduced activation of portal fibroblast [116] Acellular human amniotic membrane CCL 4 treated mice Functional acellular human amniotic membrane-hepatocytes grafts integrated with the liver decreases the acute liver injury of mice [79] Table 1. Cont.…”