Elucidation of the liver pathophysiology of COVID-19 patients using liver-on-a-chips

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  • Deguchi, Sayaka
    Center for iPS Cell Research and Application (CiRA), Kyoto University; Department of Medical Science, Graduate School of Medicine, Kyoto University
  • Kosugi, Kaori
    Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Hashimoto, Rina
    Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Sakamoto, Ayaka
    Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Yamamoto, Masaki
    Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University
  • Krol, Rafal P
    CiRA Foundation, Research and Development Center
  • Gee, Peter
    MaxCyte, Inc.
  • Negoro, Ryosuke
    Laboratory of Molecular Pharmacokinetics, College of Pharmaceutical Sciences, Ritsumeikan University
  • Noda, Takeshi
    Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University; CREST, Japan Science and Technology Agency (JST)
  • Yamamoto, Takuya
    Center for iPS Cell Research and Application (CiRA), Kyoto University; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University; Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP)
  • Torisawa, Yu-suke
    Department of Micro Engineering, Kyoto University
  • Nagao, Miki
    Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University
  • Takayama, Kazuo
    Center for iPS Cell Research and Application (CiRA), Kyoto University; AMED-CREST, Japan Agency for Medical Research and Development (AMED)
  • David Brenner
    editor

Description

SARS-CoV-2 induces severe organ damage not only in the lung but also in the liver, heart, kidney, and intestine. It is known that COVID-19 severity correlates with liver dysfunction, but few studies have investigated the liver pathophysiology in COVID-19 patients. Here, we elucidated liver pathophysiology in COVID-19 patients using organs-on-a-chip technology and clinical analyses. First, we developed liver-on-a-chip (LoC) which recapitulating hepatic functions around the intrahepatic bile duct and blood vessel. We found that hepatic dysfunctions, but not hepatobiliary diseases, were strongly induced by SARS-CoV-2 infection. Next, we evaluated the therapeutic effects of COVID-19 drugs to inhibit viral replication and recover hepatic dysfunctions, and found that the combination of anti-viral and immunosuppressive drugs (Remdesivir and Baricitinib) is effective to treat hepatic dysfunctions caused by SARS-CoV-2 infection. Finally, we analyzed the sera obtained from COVID-19 patients, and revealed that COVID-19 patients, who were positive for serum viral RNA, are likely to become severe and develop hepatic dysfunctions, as compared with COVID-19 patients who were negative for serum viral RNA. We succeeded in modeling the liver pathophysiology of COVID-19 patients using LoC technology and clinical samples.

Journal

  • PNAS Nexus

    PNAS Nexus 2 (3), pgad029-, 2023-03

    Oxford University Press (OUP)

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