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Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue

Author

Listed:
  • Sewoom Baek

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Hyun-Su Ha

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Jeong Su Park

    (Yonsei University College of Medicine)

  • Min Jeong Cho

    (Catholic University of Korea, Seoul St. Mary’s Hospital)

  • Hye-Seon Kim

    (Yonsei University College of Medicine
    Brigham and Women’s Hospital, Harvard Medical School)

  • Seung Eun Yu

    (Yonsei University College of Medicine)

  • Seyong Chung

    (Yonsei University College of Medicine)

  • Chansik Kim

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Jueun Kim

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Ji Youn Lee

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

  • Yerin Lee

    (Yonsei University College of Medicine)

  • Hyunjae Kim

    (Yonsei University College of Medicine)

  • Yujin Nam

    (Yonsei University College of Medicine)

  • Sungwoo Cho

    (Yonsei University College of Medicine)

  • Kyubae Lee

    (Konyang University)

  • Ja Kyung Yoon

    (Yonsei University College of Medicine)

  • Jin Sub Choi

    (Yonsei University College of Medicine)

  • Dai Hoon Han

    (Yonsei University College of Medicine)

  • Hak-Joon Sung

    (Yonsei University College of Medicine
    Yonsei University College of Medicine)

Abstract

Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions.

Suggested Citation

  • Sewoom Baek & Hyun-Su Ha & Jeong Su Park & Min Jeong Cho & Hye-Seon Kim & Seung Eun Yu & Seyong Chung & Chansik Kim & Jueun Kim & Ji Youn Lee & Yerin Lee & Hyunjae Kim & Yujin Nam & Sungwoo Cho & Kyub, 2024. "Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49386-8
    DOI: 10.1038/s41467-024-49386-8
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    References listed on IDEAS

    as
    1. Jung Bok Lee & Dae-Hyun Kim & Jeong-Kee Yoon & Dan Bi Park & Hye-Seon Kim & Young Min Shin & Wooyeol Baek & Mi-Lan Kang & Hyun Jung Kim & Hak-Joon Sung, 2020. "Microchannel network hydrogel induced ischemic blood perfusion connection," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
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