Effects of human amnion-derived mesenchymal stem cells and conditioned medium in rats with sclerosing cholangitis.

ABSTRACT

Mesenchymal stem cells (MSCs) represent a valuable cell source in regenerative medicine, and large numbers of MSCs can be isolated from the amnion noninvasively. Sclerosing cholangitis is a chronic cholestatic disease and characterized by progressive biliary destruction leading to cirrhosis. Many factors are involved in the development of sclerosing cholangitis; however, effective medical therapy is not established. We investigated the effects of human amnion-derived MSCs (hAMSCs) and conditioned medium (CM) obtained from hAMSC cultures in rats with sclerosing cholangitis. Sclerosing cholangitis was induced via the intragastric administration of 100 mg/kg alpha-naphthylisothiocyanate (ANIT) twice weekly for 4 weeks. One million hAMSCs or 200 µL of CM were intravenously administered on days 15 and 22. Rats were sacrificed on day 29 and evaluated via histological, immunohistochemical, and mRNA expression analyses. hAMSC transplantation and CM administration significantly improved the histological score. In addition, these two interventions significantly improved biliary hyperplasia, peribiliary fibrosis, and inflammation in Glisson's sheath. Accordingly, CK19, MMP-9, and TNF-α, and MCP-1 expression in the liver was also decreased by hAMSC and CM administration. In conclusion, hAMSC and CM administration ameliorated biliary hyperplasia, peribiliary fibrosis, and inflammation in a rat model of sclerosing cholangitis. hAMSCs and CM may represent new modalities for treating sclerosing cholangitis.