Organoid systems to study the effect of steroid in modulating immune-mediated inflammation in biliary atresia: A bridge to therapeutic application

Dr Chung, Ho Yu   (Principal Investigator (PI))

Emeritus Professor Tam Paul Kwong Hang   (Co-Investigator)

Professor Wong Kenneth Kak Yuen   (Co-Investigator)

Dr Lui Chi Hang   (Co-Investigator)

36

2021-12-01

1394170

Organoid systems to study the effect of steroid in modulating immune-mediated inflammation in biliary atresia: A bridge to therapeutic application

Biliary atresia, Hepatology, Kasai portoenterostomy, Liver organoid, Steroid, Toll-like receptors

Others - Medicine, Dentistry and Health

08191976

Health and Medical Research Fund - Full Grant

2020

On-going

Objective The objective of this study is to explore the effect of steroid in modulating immune-mediated inflammatory response in biliary atresia (BA) Hypothesis to be tested This study tests the hypothesis that steroid could alter the expression of toll-like receptors and inflammatory genes in cholangiocytes and mitigate aberrant morphological changes in human and animal BA samples. Design and subjects This project compromises in-vitro and in-vivo studies on the inflammatory pathway of BA. Morphological and RNA sequencing analysis will be performed on liver organoids obtained from i) BA liver samples collected at the time of Kasai operation (human BA model) and ii) liver biopsy sample from Rhesus rotavirus A-infected mice (RRA-mice, animal BA model). These samples will be treated with steroid and their changes before and after treatment will be analyzed. Study instruments RNA sequencing; real-time quantitative PCR; flow cytometry Interventions Human BA organoids will be co-cultured with prednisolone 1µg/ml starting from culture day 3 for 2 weeks. RRA-mice will be intraperitoneally injected Prednisolone (three times per week with 4mg/kg body weight) from post-RRA day 20 until the day of sacrifice Main outcome measured The main outcome is the difference in the expression of toll-like receptors, inflammatory genes and morphology in the liver organoids from human as well as RRA-mice model before and after treatment. In addition, phenotypical and biochemical changes at various time points in RRA-mice will also be measured. Expected results It is expected that steroids could modulate inflammation and ameliorate aberrant morphology in pre-operative BA samples.