Reply to: “Stop using the misidentified cell line LO2 as a human hepatocyte”
Authors: Qian Song, Xiang Zhang, Jun Yu
Journal: Journal of Hepatology (2024)

Stop using the misidentified cell line LO2 as a human hepatocyteJournal of HepatologyVol. 80Issue 5PreviewRecently, we read the article by Song et al. in the Journal of Hepatology.1 Using cellular and animal models, the authors concluded that B. pseudolongum protected against non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC) by secreting the antitumor metabolite acetate through the gut-liver axis, and thus, suggested that B. pseudolongum is a potential probiotic for NAFLD-HCC prevention. Undoubtedly, the results of this study are very promising regarding a novel probiotic for the potential prevention and treatment of NAFLD-HCC in humans. Full-Text PDF Bifidobacterium pseudolongum-generated acetate suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinomaJournal of HepatologyVol. 79Issue 6PreviewRecent studies have highlighted the role of the gut microbiota and their metabolites in non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). We aimed to identify specific beneficial bacterial species that could be used prophylactically to prevent NAFLD-HCC. Full-Text PDF Open Access We appreciate the comment by Shao and Chen,1Shao T. Chen Y.L. Stop using the misidentified cell line - LO2 as a human hepatocyte.J Hepatol. 2023; Abstract Full Text Full Text PDF Google Scholar with reference to our recent paper,2Song Q. Zhang X. Liu W. et al.Bifidobacterium pseudolongum-generated acetate suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma.J Hepatol. 2023; 79: 1352-1365Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar that LO23Miyazaki K. Takaki R. Nakayama F. et al.Isolation and primary culture of adult human hepatocytes. Ultrastructural and functional studies.Cell Tissue Res. 1981; 218: 13-21Crossref PubMed Scopus (25) Google Scholar might be a misidentified cell line not representative of normal human hepatocyte. We have performed additional assays using THLE-2 cells, a well-established normal human hepatocyte cell line.4Pfeifer A.M. Cole K.E. Smoot D.T. et al.Simian virus 40 large tumor antigen-immortalized normal human liver epithelial cells express hepatocyte characteristics and metabolize chemical carcinogens.Proc Natl Acad Sci U S A. 1993; 90: 5123-5127Crossref PubMed Scopus (215) Google Scholar We showed that Bifidobacterium pseudolongum conditioned medium (B.p CM) had no discernible effect on cell proliferation, cell apoptosis, and cell cycle progression in THLE-2 cells (Fig. 1). These findings reinforce our original observation that B.p CM selectively inhibited the growth of non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC) cell lines (HKCI-2 and HKCI-10), while having no significant effect on normal hepatocytes. The authors received no financial support to produce this manuscript. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. QS performed the experiments and drafted the manuscript. XZ revised the manuscript. JY supervised the study and revised the manuscript. The following are the supplementary data to this article: Download .pdf (.26 MB) Help with pdf files Multimedia component 1