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Introduction Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced pluripotent stem cells (hiPSCs) and a rat decellularized liver serving as a scaffold. Methods Rat liver harvesting and decellularization were performed as reported in our previous studies. The decellularized liver scaffold was recellularized with hiPSC-derived hepatocyte-like cells (hiPSC-HLCs) through the biliary duct. The recellularized liver graft was continuously perfused with the culture medium using a pump at a flow rate of 0.5 mL/min in a standard CO2 (5%) cell incubator at 37 °C. Results After 48 h of continuous perfusion culture, the hiPSC-HLCs of the recellularized liver distributed into the parenchymal space. Furthermore, the recellularized liver expressed the albumin (ALB) and CYP3A4 genes, and secreted human ALB into the culture medium. Conclusion Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions., Highlights • Human iPSC-derived hepatocytes were engrafted in a rat decellularized liver scaffold. • The recellularized liver expressed human liver-related markers ALB and CYP3A4. • The recellularized liver scaffold secreted human albumin. • This novel model shows potential for artificial whole liver transplantation.

The current lack of an easily measurable surrogate marker of cancer stem cells (CSCs) prevents the clinical application of CSCs for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC‐CSC marker associated with transforming growth factor beta (TGFβ)/Smad signaling, and that K19+ HCC‐CSCs could be a new therapeutic target of TGFβ receptor 1 inhibitor LY2157299. In this study, we examined whether K19+ HCC‐CSCs can be tracked using cytokeratin 19 fragment CYFRA 21‐1. In 147 HCC patients who underwent curative resection and evaluated K19 expression by immunohistochemistry, preoperative serum CYFRA 21‐1 levels were significantly higher in K19+ patients than in K19− patients (P

Liver fibrosis is characterized by the progressive accumulation of extracellular matrix (ECM) and is a strong predictor of hepatocellular carcinoma (HCC) development and progression. However, the effect of ECM in fibrotic livers on HCC cells is poorly understood. The aims of this study were to create a new culture system that retained the natural ECM of fibrotic model livers and to establish whether natural ECM regulated the characteristics of HCC cells. Using an organ decellularization technique, we created a new culture system that preserved the tissue-specific ECM of fibrotic model livers from CCl4-treated rats. The content of ECM in fibrotic model liver scaffolds was increased and the ECM microstructure was distorted. Quantitative polymerase chain reaction and immunofluorescence assays of HCC cells cultured in fibrotic model liver scaffolds for 7 days showed an epithelial-mesenchymal transition phenotype. Moreover, the ECM of fibrotic model livers promoted proliferation and chemoresistance of HCC cells. These results showed a novel effect of natural ECM in fibrotic model livers on the malignant behaviour of HCC cells. This new culture system will be useful for both understanding the cell biology of fibrotic livers and developing novel anti-cancer drugs.

We report here a rare case of a patient with recurrent intrahepatic cholangiocarcinoma that was treated with simple S-1 chemotherapy, who is still alive 6 years later. A liver tumor was identified in segments 5 to 6 in a 60-year-old male asymptomatic hepatitis B carrier. The tumor was diagnosed as hepatocellular carcinoma by MRI and CT. However, following its resection by extended posterior segmentectomy of the liver, pathological findings identified it as an intrahepatic cholangiocarcinoma. The surgical margin was cancer-negative. No additional adjuvant chemotherapy was administered because of the patient 's impaired renal function. When tumor recurrence was found by MRI 30 months later, an additional liver resection was planned but a laparotomy was eventually performed. This was because intraoperative findings revealed Glissonian sheath invasion with involvement of the umbilical portion. S-1 treatment(100mg/body/day)was started. Although the dose had to be reduced(mostly 75mg/body/day)due to hyperbilirubinemia and there were some interruptions in the regimen, in total of 42 g of S-1 was administered. The patient is currently still alive, 6 years after the detection of the tumor recurrence. This represents a rare case in patients with intrahepatic cholangiocarcinoma.