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Human amnion epithelial cells and their soluble factors reduce liver fibrosis in murine non‐alcoholic steatohepatitis
Author(s) -
Kuk Nathan,
Hodge Alexander,
Sun Ying,
Correia Jeanne,
Alhomrani Majid,
Samuel Chrishan,
Moore Gregory,
Lim Rebecca,
Sievert William
Publication year - 2019
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.14643
Subject(s) - steatohepatitis , medicine , steatosis , fibrosis , inflammation , cirrhosis , amnion , fatty liver , hepatic stellate cell , alcoholic liver disease , pathology , endocrinology , biology , disease , pregnancy , fetus , genetics
Background and Aim Non‐alcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma. Currently, lifestyle modification is the only effective treatment. We have shown that human amnion epithelial cells (hAECs) reduce inflammation and fibrosis in toxin‐induced liver injury models. We examined the effect of these cells and the soluble factors released by the cells into culture medium (hAEC conditioned medium [hAEC‐CM]) in a diet‐induced murine NASH model. Methods C57BL/6J male mice received a Western “fast food diet” for 42 weeks. Group 1 received an intraperitoneal injection of 2 × 10 6 hAECs at week 34, group 2 received an additional hAEC dose at week 38, and group 3 received thrice weekly hAEC‐CM injections intraperitoneal for 8 weeks from week 34. Liver fibrosis area, inflammation, and fibrosis regulators were measured by immunohistochemistry, qPCR, and gelatin zymography. Metabolic parameters were also assessed. Results Fast food diet‐fed mice demonstrated peri‐cellular hepatic fibrosis, inflammation, and steatosis typical of NASH. Liver fibrosis area was reduced by 40% in hAEC‐treated and hAEC‐CM‐treated mice. hAEC treatment significantly reduced pSMAD 2/3 signaling and the number of activated hepatic stellate cells and liver macrophages. Matrix metalloproteinase 2 and 9 gene and protein expression were variably affected. hAEC treatment did not alter the NASH activity score or metabolic parameters such as bodyweight, total cholesterol, or glucose tolerance. Conclusion Human amnion epithelial cell and hAEC‐CM significantly reduced hepatic inflammation and fibrosis in a diet‐induced non‐alcoholic fatty liver disease model. Although hAEC and hAEC‐CM did not affect the metabolic components of NASH, their therapeutic potential is promising and warrants further investigation.