Anti-fibrotic effects of human amniotic membrane transplantation in established biliary fibrosis induced in rats

Luciana B. Sant’Anna, Raduan Hage, Maria Angélica G. Cardoso, Emilia A. L. Arisawa, Maria Martin Cruz, Ornella Parolini, Anna Cargnoni, Nilson Sant’Anna

Risultato della ricerca: Contributo in rivistaArticolo in rivista

19 Citazioni (Scopus)


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 know 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 for its antiinflammatory, antiscarring, and wound-healing effects. We have recently shown that AM used as a patch onto the liver surface at the same time of fibrosis induction significantly reduces the progression and severity of biliary fibrosis. Here, we have investigated the effects of human AM on the already established liver fibrosis induced in rats by the bile duct ligation (BDL). We also explored the action of AM on the expression of the transforming growth factor (TGF)-β1, the main profibrogenic factor in hepatic fibrosis, and the pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and anti-inflammatory cytokine, IL-10. After 2 weeks from 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 the CellProfiler digital image analysis to quantify the area occupied by collagen deposition, ductular reaction, activated myofibroblasts, and TGF-β1. The hepatic cytokines were determined by ELISA. AM-treated rats showed a significantly lower score compared to the control BDL rats (2.5 ± 0.9 versus 3.5 ± 0.3; p<0.05), respectively. The collagen deposition, ductular reaction, 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-β1 and IL-6.
Lingua originaleEnglish
pagine (da-a)2245-2257
Numero di pagine13
RivistaCell Transplantation
Stato di pubblicazionePubblicato - 2016


  • Amniotic Membrane
  • Bile Duct Ligation
  • Digital image analysis
  • Immunohistochemistry


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