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Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue.
Baek, Sewoom; Ha, Hyun-Su; Park, Jeong Su; Cho, Min Jeong; Kim, Hye-Seon; Yu, Seung Eun; Chung, Seyong; Kim, Chansik; Kim, Jueun; Lee, Ji Youn; Lee, Yerin; Kim, Hyunjae; Nam, Yujin; Cho, Sungwoo; Lee, Kyubae; Yoon, Ja Kyung; Choi, Jin Sub; Han, Dai Hoon; Sung, Hak-Joon.
Affiliation
  • Baek S; Department 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.
  • Ha HS; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Park JS; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Cho MJ; Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Kim HS; Department of Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Yu SE; Department of Clinical Pharmacology & Therapeutics, Catholic University of Korea, Seoul St. Mary's Hospital, 222, BanpoDaero, Seocho-gu, Seoul, 06591, Republic of Korea.
  • Chung S; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Kim C; Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Kim J; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Lee JY; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Lee Y; Department 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.
  • Kim H; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Nam Y; Department 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.
  • Cho S; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Lee K; Department 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.
  • Yoon JK; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Choi JS; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Han DH; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
  • Sung HJ; Department of Medical Engineering, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Nat Commun ; 15(1): 5117, 2024 Jun 15.
Article in En | MEDLINE | ID: mdl-38879551
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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oxygen / Carcinoma, Hepatocellular / Tumor Microenvironment / Liver Neoplasms Limits: Animals / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oxygen / Carcinoma, Hepatocellular / Tumor Microenvironment / Liver Neoplasms Limits: Animals / Female / Humans / Male / Middle aged Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2024 Document type: Article Country of publication: