Cellartis iPS Cell to Hepatocyte Differentiation System citation list

Hepatocytes derived from human induced pluripotent stem (hiPS) cells using the Cellartis iPS Cell to Hepatocyte Differentiation System are an alternative to primary hepatocytes, as they exhibit sufficient expression levels of drug-metabolizing enzymes and transporters, and demonstrate stable functionality over time in culture. In addition, hiPS cell-derived hepatocytes can provide an accurate reflection of the metabolic diversity observed in the human population. Cells produced with the system are ideal for disease modeling, in vitro drug discovery and screening, metabolic studies, and toxicity testing. Read below for a citation list of studies in which the Cellartis iPS Cell to Hepatocyte Differentiation System was used in peer-reviewed basic, translational, preclinical, and biomedical research.

• Asplund, A. et al. One standardized differentiation procedure robustly generates homogenous hepatocyte cultures displaying metabolic diversity from a large panel of human pluripotent stem cells. Stem Cell Rev. 12, 90–104 (2016).

25 hPSC lines were cultured in the DEF-CS system and then successfully differentiated into hepatocytes using the Cellartis iPS Cell to Hepatocyte Differentiation System. The hepatocyte cultures were homogeneous, and the cells had functional CYP enzymes and displayed interindividual variation characteristic of primary hepatocytes obtained from different donors. 

• Ghosheh, N. et al. Highly synchronized expression of lineage-specific genes during in vitro hepatic differentiation of human pluripotent stem cell lines. Stem Cells Int. 2016:8648356 (2016).

Human induced pluripotent stem cells were thawed, maintained, and passaged in the DEF-CS system, then differentiated into hepatocytes using the Cellartis iPS Cell to Hepatocyte Differentiation System. During the differentiation process, key lineage-specific genes were analyzed by RT-qPCR, and the results showed that the gene expression profiles were highly synchronized across cell lines. Functionality of the iPS-derived hepatocytes was confirmed by measuring CYP enzyme activity, glycogen storage, and expression of drug transporters.

• Kamiya, A. et al. An in vitro model of polycystic liver disease using genome-edited human inducible pluripotent stem cells. Stem Cell Res. 32, 17–24 (2018).

Human induced pluripotent stem cells were maintained in the DEF-CS system, then differentiated into hepatic progenitor cells using the Cellartis iPS Cell to Hepatocyte Differentiation System. The researchers wanted to better understand the cell signals regulating cholangiocytic cyst formation, and were able to identify cytokines and signal inhibitors that affected cyst formation. 

• Mitra, B. et al. Hepatitis B virus precore protein p22 inhibits alpha interferon signaling by blocking STAT nuclear translocation. J Virol. 93, e0016–19 (2019).

The authors used Cellartis Hepatocyte Maintenance Medium (Cat. No. Y30051) to enhance HBV infectivity. First, the authors cultured HepG2-NTCP cells (HepG2 cells expressing human NTCP, which is a receptor that makes them susceptible to HBV infection) in DMEM. 24 hours prior to infection, the culture medium was switched to Cellartis Hepatocyte Maintenance Medium. 24 hours after infection, the medium was removed and replaced with the authors' regular maintenance medium.

• Pradip, A. et al. High content analysis of human pluripotent stem cell derived hepatocytes reveals drug induced steatosis and phospholipidosis. Stem Cells Int. 2016:2475631 (2016).

Human induced pluripotent stem cells were maintained and cultured in the DEF-CS system, followed by differentiation into hepatocytes using the Cellartis iPS Cell to Hepatocyte Differentiation System. The iPS-derived hepatocytes were exposed to drugs known to cause hepatotoxicity through steatosis and phospholipidosis. The study shows that these iPS-derived hepatocytes can be used as a platform for monitoring drug-induced steatosis and phospholipidosis by high content analysis (HCA).