Chip collection of hepatocellular carcinoma based on O 2 heterogeneity from patient tissue

• Published in: Nature communications Vol. 15; no. 1; p. 5117
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England 15.06.2024
• Subjects: Animals; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Female; Humans; Lab-On-A-Chip Devices; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mice; Middle Aged; Oxygen - metabolism; Tumor Microenvironment; Xenograft Model Antitumor Assays
• ISSN: 2041-1723

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.