PMID- 34321089 OWN - NLM STAT- MEDLINE DCOM- 20210806 LR - 20210806 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 12 IP - 1 DP - 2021 Jul 28 TI - Addressing the liver progenitor cell response and hepatic oxidative stress in experimental non-alcoholic fatty liver disease/non-alcoholic steatohepatitis using amniotic epithelial cells. PG - 429 LID - 10.1186/s13287-021-02476-6 [doi] LID - 429 AB - BACKGROUND: Non-alcoholic fatty liver disease is the most common liver disease globally and in its inflammatory form, non-alcoholic steatohepatitis (NASH), can progress to cirrhosis and hepatocellular carcinoma (HCC). Currently, patient education and lifestyle changes are the major tools to prevent the continued progression of NASH. Emerging therapies in NASH target known pathological processes involved in the progression of the disease including inflammation, fibrosis, oxidative stress and hepatocyte apoptosis. Human amniotic epithelial cells (hAECs) were previously shown to be beneficial in experimental models of chronic liver injury, reducing hepatic inflammation and fibrosis. Previous studies have shown that liver progenitor cells (LPCs) response plays a significant role in the development of fibrosis and HCC in mouse models of fatty liver disease. In this study, we examined the effect hAECs have on the LPC response and hepatic oxidative stress in an experimental model of NASH. METHODS: Experimental NASH was induced in C57BL/6 J male mice using a high-fat, high fructose diet for 42 weeks. Mice received either a single intraperitoneal injection of 2 x 10(6) hAECs at week 34 or an additional hAEC dose at week 38. Changes to the LPC response and oxidative stress regulators were measured. RESULTS: hAEC administration significantly reduced the expansion of LPCs and their mitogens, IL-6, IFNgamma and TWEAK. hAEC administration also reduced neutrophil infiltration and myeloperoxidase production with a concurrent increase in heme oxygenase-1 production. These observations were accompanied by a significant increase in total levels of anti-fibrotic IFNbeta in mice treated with a single dose of hAECs, which appeared to be independent of c-GAS-STING activation. CONCLUSIONS: Expansion of liver progenitor cells, hepatic inflammation and oxidative stress associated with experimental NASH were attenuated by hAEC administration. Given that repeated doses did not significantly increase efficacy, future studies assessing the impact of dose escalation and/or timing of dose may provide insights into clinical translation. CI - (c) 2021. The Author(s). FAU - Goonetilleke, Mihiri AU - Goonetilleke M AD - Centre for Inflammatory Disease, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia. AD - The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia. FAU - Kuk, Nathan AU - Kuk N AD - Centre for Inflammatory Disease, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia. AD - Gastroenterology and Hepatology Unit, Monash Health, Melbourne, Victoria, Australia. FAU - Correia, Jeanne AU - Correia J AD - Centre for Inflammatory Disease, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia. AD - The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia. AD - Gastroenterology and Hepatology Unit, Monash Health, Melbourne, Victoria, Australia. FAU - Hodge, Alex AU - Hodge A AD - Centre for Inflammatory Disease, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia. AD - Gastroenterology and Hepatology Unit, Monash Health, Melbourne, Victoria, Australia. FAU - Moore, Gregory AU - Moore G AD - Centre for Inflammatory Disease, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia. AD - Gastroenterology and Hepatology Unit, Monash Health, Melbourne, Victoria, Australia. FAU - Gantier, Michael P AU - Gantier MP AD - Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia. AD - Centre for Innate Immunity and Infectious Disease, Hudson Institute of Medical Research, Melbourne, Victoria, Australia. FAU - Yeoh, George AU - Yeoh G AD - Centre for Medical Research, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia. AD - School of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia. AD - Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, Australia. FAU - Sievert, William AU - Sievert W AD - Centre for Inflammatory Disease, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia. AD - Gastroenterology and Hepatology Unit, Monash Health, Melbourne, Victoria, Australia. FAU - Lim, Rebecca AU - Lim R AUID- ORCID: 0000-0002-0410-497X AD - The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia. Rebecca.Lim@monash.edu. AD - Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia. Rebecca.Lim@monash.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210728 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 SB - IM MH - Animals MH - *Carcinoma, Hepatocellular/metabolism MH - Diet, High-Fat MH - Disease Models, Animal MH - Epithelial Cells MH - Liver/metabolism MH - *Liver Neoplasms/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - *Non-alcoholic Fatty Liver Disease/metabolism MH - Oxidative Stress MH - Stem Cells PMC - PMC8317377 OTO - NOTNLM OT - Amnion epithelial cells OT - Fatty liver disease OT - Hepatic oxidative stress OT - Liver progenitor cells OT - NASH/NAFLD OT - Regenerative medicine COIS- The authors declare that they have no competing interests. EDAT- 2021/07/30 06:00 MHDA- 2021/08/07 06:00 PMCR- 2021/07/28 CRDT- 2021/07/29 05:41 PHST- 2020/10/26 00:00 [received] PHST- 2021/06/26 00:00 [accepted] PHST- 2021/07/29 05:41 [entrez] PHST- 2021/07/30 06:00 [pubmed] PHST- 2021/08/07 06:00 [medline] PHST- 2021/07/28 00:00 [pmc-release] AID - 10.1186/s13287-021-02476-6 [pii] AID - 2476 [pii] AID - 10.1186/s13287-021-02476-6 [doi] PST - epublish SO - Stem Cell Res Ther. 2021 Jul 28;12(1):429. doi: 10.1186/s13287-021-02476-6.