Page 10 - R. Organoid

[R. Organoid-5]

Human pluripotent stem cell-derived hepatic organoids as a

screening platform for toxicity prediction and drug

evaluation

Seon Ju Mun¹˙², Jaeseo Lee¹, Mi-Ok Lee¹˙², Ye Seul Son¹˙², Soo Jin Oh³, Hyun-Soo Cho¹˙², Mi-Young Son¹˙²,

Dae-Soo Kim²˙⁴, Ho-Joon Lee¹, Janghwan Kim¹˙², Cho-Rok Jung¹˙², Kyung-Sook Chung¹˙²˙⁵˙*, Myung Jin Son¹˙²˙*

¹Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon
34141, Republic of Korea, ²Department of Functional Genomics, Korea University of Science & Technology (UST), Daejeon
34113, Republic of Korea, ³Convergence Medicine Research Center, Asan Medical Center, University of Ulsan College of

Medicine, Seoul 05505, Republic of Korea, ⁴Environmental Diseases Research Center, Korea Research Institute of Bioscience
and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea, ⁵Biomedical Translational Research Center, Korea Research
Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea

The development of hepatic models capable of long-term expansion with competent liver functionality in a
personalized setting is technically challenging. Stem cell-based organoid technologies can provide an alternative

source of patient-derived primary hepatocytes. However, self-renewing and functionally competent human
pluripotent stem cell (PSC)-derived hepatic organoids are still lacking. We developed a novel method to efficiently

and reproducibly generate functionally mature human hepatic organoids derived from PSCs. The maturity of the
organoids was validated by a detailed transcriptome analysis and functional performance assays. With further

maturation, their molecular features approximated those of liver tissue. The organoids exhibited significant toxic
responses to clinically relevant concentrations of drugs that had been withdrawn from the market due to

hepatotoxicity and recapitulated human disease phenotypes such as hepatic steatosis. Therefore, these data
demonstrate that our organoids exhibit self-renewal while maintaining their mature hepatic characteristics over

long-term culture, and they may provide a versatile and valuable platform for physiologically and pathologically
relevant hepatic models in the context of personalized medicine.