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

Abstract

Liver fibrosis is the most common outcome of chronic liver diseases, and its progression to cirrhosis can only be effectively treated with liver transplantation. The amniotic membrane (AM) has been studied as an alternative therapy for fibrosis diseases mainly for its favorable properties, including anti-inflammatory, anti-scaring and immunomodulatory properties. It was recently demonstrated that the AM reduces the progression of biliary fibrosis to its advanced stage, cirrhosis, when applied on the liver for 6 weeks after fibrosis induction. Here, we investigated the effects of AM on rat fibrotic liver, during a prolonged period of time. Fibrosis was induced by bile duct ligation (BDL), and at the same time, a fragment of AM was applied around the liver. After 1, 3, 6, and 9 weeks, the degree of fibrosis was assessed by qualitative Knodell scoring, and by quantitative image analysis to quantify the area of collagen deposition in hepatic tissue. While fibrosis progressed rapidly in untreated BDL animals, leading to cirrhosis within 6 weeks, AM-treated livers showed confined fibrosis at the periportal area with few and thin fibrotic septa, but without cirrhosis. In addition, collagen deposition was reduced to about 36 and 55% of levels observed in BDL at 6 and 9 weeks after BDL, respectively, which shows that the longer the period of AM application, the lower the collagen deposition. These results suggested that AM applied as a patch onto the liver surface for longer periods attenuated the severity of biliary fibrosis and protected against liver degeneration caused by excessive collagen deposition.

Effects of Preservation Methods in the Composition of the Placental and Reflected Regions of the Human Amniotic Membrane

“…The authors observed the absence of acute rejection when the intact membrane or cells were applied. Our previous studies demonstrated the beneficial effects of fresh human AM (hAM) in animal models of ischemic heart [Cargnoni et al, 2009] and hepatic fibrosis [Sant'Anna et al, 2011;Sant'Anna et al, 2016;Sant'Anna et al, 2017]. However, concerns regarding safety and feasibility/logistics remain about the use of fresh membranes in the clinic.…”

Effects of the application of the amniotic membrane in the healing process of skin wounds in rats

“…We emphasize that the use of the HAM offers the advantages of high availability, ease of application, and good storability [12][13][14][15][16][17][18] . In this context, it is possible to affirm that by presenting properties that favor the re-structuring of the damaged portions of the tissues, the amniotic membrane could be used as a biological coverage of acute and chronic wounds [18][19][20][21][22][23][24][25][26] .…”

“…Meller et al 6 , Tahan and Tahan 8 , and Sant'Anna et al 23 , demonstrated that the HAM exerts beneficial actions in the repair and regeneration of tissues owing to its antiinflammatory, analgesic, anti-bacterial, reepithelization, and healing effects on wounds.…”

Dehydrated human amnion/chorion membrane allograft for preventing epidural fibrosis after laminectomy: an experimental rat model

“…In addition to containing many growth factors, antivasculogenic factors, and anti-inflammatory cytokines, HAMs have low immunogenicity. HAMs have been extensively employed in medical fields such as ophthalmology and for treating conditions such as bone defects, skin burns, and bladder or oral cavity reconstruction [16,17]. However, fresh amniotic membrane carries a risk of disease transmission.…”