Amniotic membrane application reduces liver fibrosis in a bile duct ligation rat model

Luciana B. Sant'Anna, Anna Cargnoni, Lorenzo Ressel, Graziella Vanosi, Ornella Parolini

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Biliary fibrosis and resultant cirrhosis are among the most common outcomes of chronic liver diseases. Currently, liver transplantation remains the only effective treatment. In seeking alternative therapeutic approaches, we focused on the potential use of the human amniotic membrane (AM). Indeed, AM has gained increasing importance for its antiscarring, anti-inflammatory, and wound-healing properties, as well as for the multipotent differentiation ability and immunomodulatory features of AM-derived cells. Intriguingly, we have recently demonstrated that placenta-derived cells reduce lung fibrosis in bleomycin-treated mice, and that AM patches reduce postischemic cardiac injury in rats. Hence, we have now investigated the effects of human AM on biliary fibrosis induced in rats through the bile duct ligation (BDL) procedure. A fragment of human AM was applied onto the liver surface after BDL and the effects on fibrosis establishment and progression were evaluated at different time points in comparison with fibrosis progression in control BDL rats. The degree of liver fibrosis was first assessed by the semiquantitative Knodell scoring system and, thereafter, by digital image morphometric analysis to quantify the area occupied by ductular reaction, activated myofibroblasts, and collagen deposition. We demonstrated a significant reduction in the severity of BDL-induced fibrosis in AM-treated rats. Indeed, while fibrosis progressed rapidly in control BDL rats, leading to cirrhosis within 6 weeks, AM-treated rats showed confined fibrosis at the portal/periportal area with no signs of cirrhosis, and a reduction in collagen deposition to about 50% of levels observed in control BDL rats. In addition, the AM was able to significantly slow the gradual progression of the ductular reaction and reduce, at all time points, the area occupied by activated myofibroblasts. These findings suggest that human AM, when applied as a patch onto the liver surface, might inhibit fibrosis progression in BDL-injured livers, and could protect against hepatic damage associated with fibrotic degeneration.
Original languageEnglish
Pages (from-to)441-453
Number of pages13
JournalCell Transplantation
Volume20
DOIs
Publication statusPublished - 2011

Keywords

  • Actins
  • Amnion
  • Animals
  • Bile Ducts
  • Collagen
  • Female
  • Humans
  • Keratin-19
  • Ligation
  • Liver Cirrhosis
  • Mice
  • Models, Animal
  • Rats
  • Rats, Wistar

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