A Korean research team has developed a three-dimensional human hepatic organoid by using stem cells and the functionally mature organoid can proliferate in human pluripotent stem cells.
A human liver is a highly regenerative organ, yet it is difficult to obtain liver tissues and in vitro liver cell proliferation is currently impossible, making liver transplantation very difficult. Besides, 2D cell-based models currently in use have their own limitations in terms of biological response reproduction and animal models cannot accurately predict human body responses due to species-specific differences. A new human body simulator has been required in this regard.
The research team, led by Professor Sohn Myung-jin at the Korea Research Institute of Bioscience and Biotechnology (KRIBB), has developed a differentiation technique for 3D organoid-type liver cell models by using human pluripotent stem cells. The liver model developed by the team can proliferate for five months or more outside a human body and shows an effective response to a drug even after freezing and thawing whereas existing pluripotent stem cell-based organoid models cannot be proliferated with ease and are functionally immature.
“Our model is superior in liver cell marker expression, albumin secretion and cell respiration to organoids based on direct separation of adults’ hepatic tissue cells,” the team explained, adding, “With our model, hepatotoxicity and efficacy assessment and prediction can be made more accurate during new drug development.” The team also said that the model is highly sensitive to drug toxicity to the point of being capable of detecting toxicity at a concentration equal to or less than an amount a human body can tolerate and a fatty liver simulation model can be produced with ease by mass and external fatty acid treatment.
Details of the research have been published in the July 9 edition of the Journal of Hepatology. The development was funded by the Big Issue Group (BIG) Project of the institute, the Ministry of Science and ICT, the National Research Foundation of Korea, and the Ministry of Health and Welfare.