Induced hepatic stem cells are suitable for human hepatocyte production

Human hepatocytes were transfected with Sendai virus vectors (SeV) express-ing OCT3/4, SOX2, KLF4, and C-MYC to produce hepatocyte-derived induced pluripotent stem cells (iPSCs). The messenger RNA (mRNA) expression of undifferentiated markers (passage 19-21) and hepatocyte-specific markers (HSMs) (passage 0-20) in 48 established hepatocyte-derived iPSC-like colonies was examined. Among the 48 clones, 10 clones continuously expressed HSM mRNA (HNF1 beta and HNF4 alpha) in passage 0-20. The colonies which expressed HSMs (iTS-L cells: induced tissue-specific stem cells from liver) showed a different tendency in microarray and methylation analyses to fibroblast-derived iPSCs (strain: 201B7). iTS-L cells were less likely to form teratomas in mice than iPSCs (He). The iTS-L cells were differentiated into hepatocyte-like cells more efficiently than iPSCs (He) or iPSCs (201B7). These data suggest that SeV ex-pressing OCT3/4, SOX2, KLF4, and C-MYC induce the generation of iPSCs and iTS-L cells.

Automated summary

Human hepatocytes were transformed into induced pluripotent stem cells (iPSCs) using Sendai virus vectors. The iPSCs expressed hepatocyte-specific markers and showed better efficiency in differentiating into hepatocyte-like cells compared to other types of iPSCs.