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. 2018 Nov 9;8(20):5562–5574. doi: 10.7150/thno.26540

Figure 4.

Figure 4

Histology and immunohistochemistry of monkey liver biopsies. (A-A”)No changes in organizational structure and cell morphology were observed in all groups before ALF. Extensive parenchymal hemorrhagic necrosis and steatosis was observed at 48 h after toxin infusion in the control group. The livers were still extensively necrotic with obvious bleeding across the entire lobule after sham treatment with a no-cell device at 48 h after toxin infusion. The numbers of hepatocytes and hepatic parenchymal cells increased significantly after SRBAL treatment at 48, 168 and 336 h after toxin infusion (H&E, ×20). (B-B”)Active caspase-3 staining for hepatocyte apoptosis was scarcely observed in healthy liver. The percentage of caspase-3-positive cellswasincreased in the ALF and sham groups at 48 h after drug infusion. In the experimental groups, the caspase-3 expression levels were lower after SRBAL treatment at the same timepoint. Caspase-3-positivestainingcan still be occasionally observed in some inflammatory cells after the repair at 168 h and 336 h (cleaved caspase-3, ×20). (C-C”) CD68 staining showed KCs liningthe walls of the sinusoids in the liver. CD68-positive cells were intensively recruited and activated after ALF induction. SRBAL treatment alleviated the overwhelming recruitment of CD68-positive cells. In the experimental groups, the levels of CD68-positive cells were lower after the treatments at 48 h after drug infusion. After the vigorous process of phagocytosis, the dead cells were cleared, and the numbers of KCs dropped back to normal (CD68, ×20).(D-D”)Staining of the regenerative marker Ki-67 wasrare in normal livers and a small numberof proliferating hepatocytes wasobserved in the remaining cells in the ALF and sham groups. Remarkable liver regeneration was observed after SRBAL treatment at 48, 168 and 336 h after toxin infusion. The SRBAL treatments with hepatocyte organoids increased significantly the percentage of proliferating cells in group A at 48 h after drug administration. The proliferation completed before 168 h. Most of the proliferated cells were locatedin the hepatocytes that had normal morphology in groupsB and C at 48 h. There were still hepatocytes proliferating at 168 h and 336 h in groupsB and group C after drug administration (Ki-67 staining, ×20and ×40).