Annals of Hepato-Biliary-Pancreatic Surgery (한국간담췌외과학회지)

The Korean Association of Hepato-Biliary-Pancreatic Surgery (한국간담췌외과학회)
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Enhancing generation efficiency of liver organoids in a collagen scaffold using human chemically derived hepatic progenitors

  • Myounghoi Kim (Department of Surgery, Hanyang University College of Medicine) ;
  • Yohan Kim (Max-Planck-Institute of Molecular Cell Biology and Genetics) ;
  • Elsy Soraya Salas Silva (Department of Surgery, Hanyang University College of Medicine) ;
  • Michael Adisasmita (Department of Surgery, Hanyang University College of Medicine) ;
  • Kyeong Sik Kim (Department of Surgery, Hanyang University College of Medicine) ;
  • Yun Kyung Jung (Department of Surgery, Hanyang University College of Medicine) ;
  • Kyeong Geun Lee (Department of Surgery, Hanyang University College of Medicine) ;
  • Ji Hyun Shin (Department of Surgery, Hanyang University College of Medicine) ;
  • Dongho Choi (Department of Surgery, Hanyang University College of Medicine)
  • Received : 2023.04.07
  • Accepted : 2023.06.08
  • Published : 2023.11.30
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Abstract

Backgrounds/Aims: Liver organoids have emerged as a powerful tool for studying liver biology and disease and for developing new therapies and regenerative medicine approaches. For organoid culture, Matrigel, a type of extracellular matrix, is the most commonly used material. However, Matrigel cannot be used for clinical applications due to the presence of unknown proteins that can cause immune rejection, batch-to-batch variability, and angiogenesis. Methods: To obtain human primary hepatocytes (hPHs), we performed 2 steps collagenase liver perfusion protocol. We treated three small molecules cocktails (A83-01, CHIR99021, and HGF) for reprogramming the hPHs into human chemically derived hepatic progenitors (hCdHs) and used hCdHs to generate liver organoids. Results: In this study, we report the generation of liver organoids in a collagen scaffold using hCdHs. In comparison with adult liver (or primary hepatocyte)-derived organoids with collagen scaffold (hALO_C), hCdH-derived organoids in a collagen scaffold (hCdHO_C) showed a 10-fold increase in organoid generation efficiency with higher expression of liver- or liver progenitor-specific markers. Moreover, we demonstrated that hCdHO_C could differentiate into hepatic organoids (hCdHO_C_DM), indicating the potential of these organoids as a platform for drug screening. Conclusions: Overall, our study highlights the potential of hCdHO_C as a tool for liver research and presents a new approach for generating liver organoids using hCdHs with a collagen scaffold.

Keywords

Acknowledgement

This work was supported by grants (NRF-2022R1A2C2004593, NRF-2021M3A9H3015390, and NRF-2022R1F1A1073058) of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (MSIT), Republic of Korea.

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