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. 2022 Mar 3;29(3):355–371.e10. doi: 10.1016/j.stem.2022.02.006

Figure 5.

Figure 5

Histological characterization in the hBEC-transplanted Krt19CreERMdm2fl/flRag2−/−Il2rg−/− biliary disease model

(A) H&E staining in the Krt19CreERMdm2fl/flRag2−/−Il2rg−/− biliary disease model reveals a pro-inflammatory profile in animals treated with PBS (PBS) and a normal parenchymal organization in the hBEC-transplanted mice (hBEC). Scale bars, 120 μm.

(B) Human anti-mitochondrial antibody immunostaining (hAMA) in tissue-derived human mesenchymal stem cell (hMSC)-transplanted Krt19CreERMdm2fl/flRag2−/−Il2rg−/− mice. Scale bars, 60 μm.

(C) hAMA immunostaining in PBS carrier (PBS) and hBEC-transplanted mice (hBEC). Far right: quantification of hBECs per total number of cells. ∗∗∗ denotes p < 0.001 (mean ± SEM), Student’s t test (n = 6 PBS and n = 7 hBECs). Scale bars, 120 μm.

(D) Immunostaining for K19 (ductular reaction), αSMA (activated hepatic stellate cells), CD45 (immune cells), HMGB1 (mediator of inflammation), and HNF4α (hepatocyte marker) in PBS carrier (PBS) and hBEC-transplanted mice (hBEC). Scale bars, 120 μm (n = 6).

(E) Quantification of the immunostainings in PBS carrier (PBS) and hBEC-transplanted mice (hBEC). Far right; quantification of HNF4α per K19+ cells. ∗ denotes p < 0.05, ∗∗ denotes p < 0.005, ∗∗∗ denotes p < 0.001 (mean ± SEM), Student’s t test (n = 6).

(F) MRCP. Sagittal section view on PBS control (PBS) and hBEC-transplanted mice (hBEC). Blue arrows indicate the position of the gallbladder, white arrows the cystic duct, and red arrows the common bile duct (CBD). Stricturing of the CBD is observed in the PBS group.

(G) Quantification of common bile duct (Ø CBD), cystic duct (Ø Cystic D), and gallbladder (Ø GB) diameters (in mm) in PBS control (PBS) and hBEC-transplanted mice (hBEC). ∗∗ denotes p < 0.005, ∗∗∗ denotes p < 0.001 (mean ± SEM), Student’s t test (n = 3).

(H) Methylene blue retrograde gallbladder injection in PBS control (PBS) and hBEC-transplanted mice (hBEC). Dashed line indicates CBD, D indicates duodenum, and the white arrow indicates the ampulla of vater (where CBD drains into the duodenum). Absence of methylene blue in the duodenum in the PBS group is indicative of obstruction in the biliary tract (n = 3).