Human amnion epithelial cells and their soluble factors reduce liver fibrosis in murine non-alcoholic steatohepatitis

Nathan Kuk, Alexander Hodge, Ying Sun, Jeanne Correia, Majid Alhomrani, Chrishan Samuel, Gregory Moore, Rebecca Lim, William Sievert

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Number of pages9
JournalJournal of Gastroenterology and Hepatology (Australia)
DOIs
Publication statusAccepted/In press - 1 Mar 2019

Keywords

  • fibrosis
  • inflammation
  • steatohepatitis
  • stem cells

Cite this

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title = "Human amnion epithelial cells and their soluble factors reduce liver fibrosis in murine non-alcoholic steatohepatitis",
abstract = "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.",
keywords = "fibrosis, inflammation, steatohepatitis, stem cells",
author = "Nathan Kuk and Alexander Hodge and Ying Sun and Jeanne Correia and Majid Alhomrani and Chrishan Samuel and Gregory Moore and Rebecca Lim and William Sievert",
year = "2019",
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Human amnion epithelial cells and their soluble factors reduce liver fibrosis in murine non-alcoholic steatohepatitis. / Kuk, Nathan; Hodge, Alexander; Sun, Ying; Correia, Jeanne; Alhomrani, Majid; Samuel, Chrishan; Moore, Gregory; Lim, Rebecca; Sievert, William.

In: Journal of Gastroenterology and Hepatology (Australia), 01.03.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Human amnion epithelial cells and their soluble factors reduce liver fibrosis in murine non-alcoholic steatohepatitis

AU - Kuk, Nathan

AU - Hodge, Alexander

AU - Sun, Ying

AU - Correia, Jeanne

AU - Alhomrani, Majid

AU - Samuel, Chrishan

AU - Moore, Gregory

AU - Lim, Rebecca

AU - Sievert, William

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

AB - 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.

KW - fibrosis

KW - inflammation

KW - steatohepatitis

KW - stem cells

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U2 - 10.1111/jgh.14643

DO - 10.1111/jgh.14643

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