Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Combined with Normothermic Machine Perfusion Repairs Bile Duct Injury in a Rat Model of DCD Liver Transplantation via Activation of Peribiliary Glands through the Wnt Pathway

Figure 4

Transformation of PBGs from a static phenotype to an active phenotype. (a) The morphology of PBGs in the sham group was intact, and cells were round with large and round nuclei located in the center of the cells (white ellipse). The morphology of PBGs in the NMP group was destroyed (red ellipse), and continuity was broken, with necrotic cells. PBGs were relatively well preserved in the BP and HBP groups, which were expanded, and a large number of proliferating cells appeared at the connecting tubes between the PBGs and the lumen of the bile ducts (blue ellipse). (b) Relative protein levels of VEGF, PCNA, caspase-3, and cleaved caspase-3 in each group were detected using western blotting (). (c) Immunofluorescence staining showed that PBGs expressed VEGFR1 and VEGFR2. (d) Expression of PCNA and caspase-3 in each group was marked by immunohistochemistry staining. Compared with the sham group (), the number of PCNA-positive cells was higher in the NMP group (, ) and even higher in the BP group (, vs. the NMP group). The increase in the HBP group was the most significant (, vs. the BP group). Compared with the sham group (), numbers of caspase-3-positive cells (, ) were significantly increased in the NMP group and decreased in the BP group (, vs. the NMP group) and further decreased in the HBP group (, vs. the BP group). , , and . PBG: peribiliary gland; NMP: normothermic machine perfusion; HBP: HO-1/BMMSCs plus NMP; BP: BMMSCs plus NMP; VEGF: vascular endothelial growth factor; PCNA: proliferating cell nuclear antigen; VEGFR1: vascular endothelial growth factor receptor 1; VEGFR2: vascular endothelial growth factor receptor 2.

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