Critical Suitability Evaluation of Caco‑2 Cells for Gut-on-a-Chip

• Published in: ACS applied materials & interfaces 2024-09, Vol.16 (38), p.51139-51149
• Main Authors: Pan, Xiatong, Chen, Jun, Han, Junlei, Zhang, Wenxian, Su, Weiguang, Xu, Zhipeng, Li, Xinyu, Song, Ming, Song, Wei, Xie, Xi, Wang, Li
• Format: Article
• Language: English
• Subjects: Functional Inorganic Materials and Devices
• ISSN: 1944-8244; 1944-8252; 1944-8252
• DOI: 10.1021/acsami.4c11409

Currently, culturing Caco-2 cells in a Gut-on-a-chip (GOC) is well-accepted for developing intestinal disease models and drug screening. However, Caco-2 cells were found to overexpress surface proteins (e.g., P-gp) compared with the normal intestinal epithelial cells in vivo. To critically evaluate the challenge and suitability of Caco-2 cells, a GOC integrated with a carcinoembryonic antigen (CEA) biosensor was developed. This three-electrode system electrochemical sensor detects CEA by antigen–antibody specific binding, and it exhibits high selectivity, excellent stability, and good reproducibility. Under dynamic culturing in the GOC, Caco-2 cells exhibited an intestinal villus-like structure and maintained tissue barrier integrity. Meanwhile, CEA was discovered to be secreted from 0 to 0.22 ng/mL during the 10-day culturing of Caco-2 cells. Especially, CEA secretion increased significantly with the differentiation of Caco-2 cells after 6 days of culturing. The sustained high-level CEA secretion may induce cells to avoid apoptotic stimuli, which faithfully reflects the efficacy of a new drug and the mechanism of intestinal disease. Different kinds of cell types (e.g., intestinal primary cells, stem cell-induced differentiation) in the GOC should be attempted for drug screening in the future.