Successful induction of human chemically induced liver progenitors with small molecules from damaged liver

Three-dimensional human bile duct formation from chemically induced human liver progenitor cells

“…In heterogeneous cell culture dishes that induce hepatic progenitor cells, it is imperative to remove a large number of mixed fibrotic cells ( Singh et al, 2013 ). It has been previously reported that many fibrotic cells produced during the induction of MHs are isolated using different culture medium ( Miyoshi et al, 2022 ). When using hCLiPs to generate BDs, fibroblasts affect the formation of BD due to the rapid proliferation of fibroblasts ( Supplementary Figure S2A ), and the hCLiPs were enriched in purity without damage by multiple subcultures ( Supplementary Figure S3A–C ).…”

“…When isolating mature hepatocytes by two-step perfusion using collagenase, fibrous cells, BD cells and other nonparenchymal cells are always mixed because of the heterogeneity of liver cells ( Zhang et al, 2016 ; Aizarani et al, 2019 ). Induction cultures are often heterogeneous because of the presence of undifferentiated derivatives and nonparenchymal cells, thereby introducing variability, potential immunogenicity, and problems in directed differentiation ( Singh et al, 2013 ; Miyoshi et al, 2022 ). When FAC medium induced hepatocyte dedifferentiation, fibroblast cells with strong growth ability grew on P0, gained a growth advantage during the passage process and interfered with the proliferation of hCLiPs after passaging, as shown in the supplemental data.…”

Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis

“…In addition, under our quantification of hepatic fibrosis in Supplementary Fig. 3 , amount of fibrosis in our CDAHFD model at 12 week showed equivalent percentage of fibrosis (15% of Azan positive) using an imaging analysis software (Win ROOF, MITANI Co., Tokyo, Japan) to clinical samples of F3-4 liver fibrosis of the patients, which were used for our previous study as a damaged liver [ 18 ]. Supplementary Table 1 shows biochemical parameters of each models at 12 weeks of each diet administration.…”

Update on Hepatobiliary Plasticity

“…Specifically, FXR activation did not only suppress LPC proliferation but also induced its death. 103 Given the correlation between LPC number and the severity of human liver diseases 21 104 and the potential of regenerative therapy to promote LPC-to-hepatocyte differentiation in the diseased livers, the third step, LPC-to-hepatocyte differentiation, was more extensively investigated using the zebrafish model than the other steps. It was revealed that BMP signaling 105 and Tel2 101 positively regulate the third step through Tbx2b and Hhex, respectively, and that Notch signaling negatively regulates the step.…”