한빛사논문
- 조회795
Lee, Jaeseo1; Gil, Dayeon2,3; Park, Hyeyeon2,3; Lee, Youngsun2,3; Mun, Seon Ju1; Shin, Yongbo1,4; Jo, Eunji5; Windisch, Marc P.5; Kim, Jung-Hyun2,3; Son, Myung Jin1,4,6
1Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
2Korea National Stem Cell Bank, 187, Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, Republic of Korea
3Division of Intractable Diseases Research, Department of Chronic Diseases Convergence Research, Korea National Institute of Health, Osong Health Technology Administration Complex 202, Republic of Korea
4Department of Functional Genomics, Korea University of Science & Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea
5Applied Molecular Virology Laboratory, Institute Pasteur Korea, Seongnam-si, Republic of Korea
6School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
Jaeseo Lee and Dayeon Gil: These authors contributed equally to this work.
Correspondence: Jung-Hyun Kim, Myung Jin Son
Abstract
Background and aims: HCV infection can be successfully managed with antiviral therapies; however, progression to chronic liver disease states, including NAFLD, is common. There is currently no reliable in vitro model for investigating host-viral interactions underlying the link between HCV and NAFLD; although liver organoids (LOs) show promise, they currently lack non-parenchymal cells, which are key to modeling disease progression.
Approach and results: Here, we present a novel, multicellular LO model using a co-culture system of macrophages and LOs differentiated from the same human pluripotent stem cells (PSCs). The co-cultured macrophages shifted towards a Kupffer-like cell type, the liver-resident macrophages present in vivo, providing a suitable model for investigating NAFLD pathogenesis. With this multicellular Kupffer-like cell-containing LO (Kp-LO) model, we found that HCV infection led to lipid accumulation in LOs by upregulating host lipogenesis, which was more marked with macrophage co-culture. Reciprocally, long-term treatment of LOs with fatty acids (FAs) upregulated HCV amplification and promoted inflammation and fibrosis. Notably, in our Kp-LO model, the effects of three drugs for NASH that have reached phase 3 clinical trials exhibited consistent results with the clinical outcomes.
Conclusions: Taken together, we introduced a multicellular LO model consisting of hepatocytes, Kupffer-like cells, and HSCs, which recapitulated host-virus intercommunication and inter-cellular interactions. With this novel model, we present a physiologically relevant system for the investigation of NAFLD progression in HCV patients.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-11-20)
- 국내 연구진
- 바이오·의료융합 > 바이오·의료융합 기타
댓글 작성 로그인
팝업 닫기관련 링크
연구자 ID
소속기관 논문보기
관련분야 논문보기
