하현수 (연세대학교 의과대학)

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연세대학교 의과대학

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Nat. Commun., Jun 15 2024, 15 (1) | https://doi.org/10.1038/s41467-024-49386-8 Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue

Sewoom Baek^1,2,10, Hyun-Su Ha^2,3,10, Jeong Su Park^4,10, Min Jeong Cho⁵, Hye-Seon Kim^2,6, Seung Eun Yu², Seyong Chung², Chansik Kim^1,2, Jueun Kim^1,2, Ji Youn Lee^1,2, Yerin Lee², Hyunjae Kim², Yujin Nam², Sungwoo Cho², Kyubae Lee⁷, Ja Kyung Yoon⁸, Jin Sub Choi⁹, Dai Hoon Han⁹& Hak-Joon Sung^1,2

¹Department of Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

²Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

³Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

⁴Department of Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

⁵Department of Clinical Pharmacology & Therapeutics, Catholic University of Korea, Seoul St. Mary’s Hospital, 222, BanpoDaero, Seocho-gu, Seoul 06591, Republic of Korea.

⁶Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.

⁷Department of Biomedical Materials, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Republic of Korea.

⁸Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Center for Clinical Imaging Data Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

⁹Department of Surgery, Division of Hepato-biliary and Pancreatic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

¹⁰These authors contributed equally: Sewoom Baek, Hyun-Su Ha, Jeong Su Park.

Corresponding authors

Correspondence to Dai Hoon Han or Hak-Joon Sung.

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.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-17)
연구진국내(교신)+국외 연구진
분야 의약학 > 재생의학

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