Table 3.
Summary and the progression of the application of organoids in liver diseases.
| Rare Liver Disease | Co-Culture Type, Species | Major Findings | Reference |
|---|---|---|---|
| ALGS | - iPSC-derived hepatocyte | - The organoids had a regenerative property that is similar to that of the human liver, and a set of mutations related to ALGS was found to have a significant effect on the pathogenesis of liver disease. | [76] |
| Biliary Atresia | - Biliary atresia-BA-like model, human-derived | - Created BA model from a non-sick individual and demonstrated drug effectiveness. | [77] |
| - The study found that beta-amyloid accumulates around bile ducts in patients’ livers. | [78] | ||
| - Organoids derived from patients revealed molecular and functional evidence of delayed epithelial development in BA patients. | [79] | ||
| Wilson’s Disease | - Derived hepatocyte, dog model | - Survival of genetically corrected autologous organoid-derived hepatocyte-like cells in vivo. | [80] |
| - Gene supplementation in hepatic organoids of COMMD1-deficient dogs restores function and can effectively cure copper storage disease. | [81] | ||
| Primary Sclerosing Cholangitis (PSC) | - Human bile duct organoid model | - Organoids recapitulate disease inflammatory immune profile. | [82] |
| - Organoids recapitulate the senescence, pro-inflammatory factors, and macrophage recruitment observed in PSC. | [83] | ||
| Infectious Diseases | |||
| HEV | - ASC human organoids inoculated with HEV particles in a transwell system | - This model can be used for drug screening, identifying new HEV inhibitors, and improving our insights to study virus–host interaction and antiviral therapies. | [84] |
| SARS-CoV-2 | - ASC human liver bile duct organoids | - Liver damage caused directly by SARS-CoV-2 infection should be valued when treating COVID-19 patients. | [85] |
| Common Diseases with Liver Model | |||
| ALF | - ASC mouse-derived model | - Human liver organoids generated with single-donor-derived multiple cells rescued mice from acute liver failure. | [86] |
| Steatohepatitis | - MOC human-derived organoid | - The model displayed genetic dysfunction of lysosomal acid lipase, which is found in severe steatohepatitis. The model can also be used to study inflammation and fibrosis in humans. | [68] |
| Ischemia | - Intrahepatic cholangiocyte organoids (ICOs), human-derived ASC | - The organoids recapitulate ischemic cholangiopathy in vitro and enable drug assessment studies for the discovery of new therapeutics for ischemic cholangiopathies. | [87] |
| NAFLD | - APOB or MTTP knockout organoids derived from human hepatocyte cell line | - This model facilitated steatosis etiology and provided a drug screening platform. | [88] |
| Diabetes Mellitus | - MOC model derived from humans | - This model showed the cellular functions of diabetic patients and their response to external stimuli and drugs. | [89] |
| Cystic Fibrosis | - ASC, human-derived, extrahepatic cholangiocyte organoids (ECOs) | - Organoid model derived from cystic fibrosis patient showed no CFTR channel activity but showed normal chloride channel and MDR1 transporter activity. | [52] |
Abbreviations: ASCs, adult stem cells; iPSCs, induced pluripotent stem cells; ALGS, Alagille syndrome; BA, biliary atresia; PSCs, primary sclerosing cholangitis; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ALF, acute liver failure; NAFLD, non-alcoholic fatty liver disease; MOC, multi-organ microfluidic chips; ICO, intrahepatic cholangiocyte organoids; ECO, extrahepatic cholangiocyte organoids.