Non-alcoholic fatty liver disease(NAFLD),a type of liver disease for which no treatment is currently approved,remains a major concern worldwide.It is manifested as simple hepatocyte steatosis and can develop into infl...Non-alcoholic fatty liver disease(NAFLD),a type of liver disease for which no treatment is currently approved,remains a major concern worldwide.It is manifested as simple hepatocyte steatosis and can develop into inflam-mation,fibrosis,cirrhosis and liver cancer in severe cases.However,due to the lack of appropriate in vitro drug testing platforms,an in-depth understanding of the therapeutic activity of ginsenoside Rb_(1)in NAFLD remains challenging.Here,we proposed a NAFLD model on a liver organoids(LOs)-on-a-chip platform to evaluate the therapeutic effect of ginsenoside Rb_(1)in a dynamic,multi-condition and high-throughput manner.This platform allowed us to reshape certain features such as multicellular types and liver-specific functions of the physiology of the human-relative liver.Free fatty acids(FFAs)-induced LOs displayed typical pathological characteristics of NAFLD progression,including steatosis,oxidative stress,lipid peroxidation,inflammation and fibrosis.With ginsenoside Rb_(1)intervention,these pathological features can be significantly improved,which may provide new insights into the potential mechanisms of NAFLD progression and treatment and suggest the clinical implications for humans.The proposed system enables the formation,differentiation,and function of LOs to serve as a scalable,high-throughput and sensitive drug testing model,to potentially expedite the NAFLD drug discovery.展开更多
基金supported by the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Projects(TSBICIP-CXRC-008)Major Project of Haihe Laboratory of Synthetic Biology(E2M9560201)+1 种基金National Natural Science Foundation of China(32301210&31200035)the China Postdoctoral Science Foundation(No.2022M713330).
文摘Non-alcoholic fatty liver disease(NAFLD),a type of liver disease for which no treatment is currently approved,remains a major concern worldwide.It is manifested as simple hepatocyte steatosis and can develop into inflam-mation,fibrosis,cirrhosis and liver cancer in severe cases.However,due to the lack of appropriate in vitro drug testing platforms,an in-depth understanding of the therapeutic activity of ginsenoside Rb_(1)in NAFLD remains challenging.Here,we proposed a NAFLD model on a liver organoids(LOs)-on-a-chip platform to evaluate the therapeutic effect of ginsenoside Rb_(1)in a dynamic,multi-condition and high-throughput manner.This platform allowed us to reshape certain features such as multicellular types and liver-specific functions of the physiology of the human-relative liver.Free fatty acids(FFAs)-induced LOs displayed typical pathological characteristics of NAFLD progression,including steatosis,oxidative stress,lipid peroxidation,inflammation and fibrosis.With ginsenoside Rb_(1)intervention,these pathological features can be significantly improved,which may provide new insights into the potential mechanisms of NAFLD progression and treatment and suggest the clinical implications for humans.The proposed system enables the formation,differentiation,and function of LOs to serve as a scalable,high-throughput and sensitive drug testing model,to potentially expedite the NAFLD drug discovery.
