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Background Can Background be changed from bold to normal text?: Chemically-induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. We aimed to clarify the efficacy of CLiPs for ameliorating fibrosis in a diet-induced nonalcoholic steatohepatitis rat model, since nonalcoholic fatty liver disease is currently recognized as the most common form of chronic liver disease in developed countries. Methods: Primary mature hepatocytes were isolated from 7-week-old male Wistar rats. To establish CLiPs, isolated hepatocytes were cultured in differentiation medium composed of Y-27632, A-83-01, and CHIR99021 (YAC medium). As an animal model that reproduces NASH pathophysiology, 6-week-old severe combined immunodeficient (SCID) mice were carefully selected and prepared and fed with choline-deficient, L-amino acid-defined, high-fat diet (HFD). After 12 weeks’ HFD feeding, the mice were assigned to continue HFD with or without the administration of rat CLiPs (HFD + CLiPs and HFD-CLiPs, respectively). Rat CLiPs were administered from the spleen. Hepatic fibrosis was semi-quantitatively evaluated according to histology. Liver parenchyma and blood samples were collected for biochemical analyses. Results: Rat CLiPs were positive for CK19 and EpCAM were successfully delivered to the liver. At 8 weeks after CLiPs transplantation, the HFD + CLiPs group showed significantly less positive staining than the HFD-CLiPs group. Alanine aminotransferase significantly improved in the HFD + CLiPs group, as demonstrated by Azan staining and αSMA immunostaining. RT qPCR showed that the liver expression of MMP2 and 9 tended to be higher in the HFD + CLiPs group. Conclusions: The anti-fibrotic effect of CLiPs was demonstrated in the immunodeficient NASH animal model and may have therapeutic applications in humans.

Aim: The formation of a secondary liver is expected in ectopic transplants in liver therapy. It is reported that the transplantation of hepatocyte sheets constitutes one of the techniques used to form a secondary liver. Accordingly, we established a subcutaneous transplant for hepatocyte/fibroblast sheets in previous studies. In this development study with hepatocyte/fibroblast sheets, we evaluated the differences in transplantation sites to promote the maturation of transplanted tissue in a liver injury model. Methods: A cocultured hepatocyte sheet of fibroblasts (TIG-118 cells) and human hepatocytes (PXB cells) was prepared on a temperature-responsive culture dish. The prepared cocultured hepatocyte sheet was either transplanted subcutaneously or on the liver surface of a persistent liver injury model (cDNA-uPA/SCID mouse: uPA mouse), and was evaluated by the human albumin concentration in mouse blood. As a control group, hepatocyte cell sheets were used that were transplanted to both areas and compared. Results: Although the cocultured hepatocyte sheet led to functional improvements in the early stages of culture in subcutaneous transplantation, these did not last in the long-term after transplantation. Although coculture effects were not observed in the liver surface transplantation case, long-term functional expressions in mono- and cocultured sheets in the case of liver surface transplantation were exhibited compared with subcutaneous administration. Conclusion: These results suggest that sustained stimulation of liver regenerationvaries depending on the transplant site and is largely involved in the maturation of hepatocyte tissue.

Summary: Background: Delayed gastric emptying (DGE) is uncomfortable complication after left hepatectomy. The aim of this study is to show our strategy to prevent DGE after living donor left hepatectomy. Methods: The cases were divided into 3 groups as without any prevention (control group), prevented DGE with putting omentum between the liver and pylorus (O group), and with putting a Seprafilm (S group). The incidence of DGE and the CT finding 1 month after surgery were retrospectively compared between the groups. Results: The incidence of DGE was significantly decreased in O and S group than control group (P

Introduction: Intraportal islet transplantation is a promising therapeutic approach for patients with type 1 diabetes mellitus (T1DM). However, despite being minimally invasive, the method has some limitations, such as short-term graft loss, portal venous thrombosis, and difficulty in collecting adequate amounts of islets. Subcutaneous islet transplantation on adipose-derived mesenchymal stem cell (ADSC) sheets has been suggested to overcome these limitations, and in this study, we have examined its feasibility in T1DM pigs. Methods: Inguinal subcutaneous fat was harvested from young pigs and then isolated and cultured adequate ADSCs to prepare sheets. Islets were isolated from the pancreases of mature pigs and seeded on the ADSC sheets. T1DM pigs were generated by total pancreatectomy, and ADSC sheets with transplanted islets were administered subcutaneously to the waist (n = 2). The effects of the islets on the ADSC sheets and on blood glucose levels were evaluated. Insulin secretion was measured by insulin stimulation index. Results: Islet viability was higher on ADSCs compared to islets alone (91.8 ± 4.3 vs. 81.7 ± 4.1%). The insulin stimulation index revealed higher glucose sensitivity of islets on ADSC sheets compared to islets alone (2.8 ± 2.0 vs. 0.8 ± 0.3). After transplantation, the blood glucose levels of two pigs were within the normal range, and sensitive insulin secretion was confirmed by intravenous glucose tolerance tests. After graftectomy, decreased insulin secretion and hyperglycemia were observed. Conclusions: Subcutaneous islet transplantation using ADSC sheets can regulate the blood glucose levels of T1DM pigs.

Introduction: Cell sheets consisting of adipose-derived stem cells (ADSCs) have been reported to be effective for wound healing. We conducted this study to clarify the efficacy of ADSC sheets in wound healing at the duct-to-duct biliary anastomotic site in pigs. Methods: Eleven female pigs (20–25 kg) were divided into two groups: biliary anastomosis with an ADSC sheet (n = 6) or without an ADSC sheet (n = 5). To follow the transplanted ADSCs, PKH26GL-labeled sheets were used in one of the ADSC pigs. Two weeks prior to laparotomy, ADSCs were isolated from the lower abdominal subcutaneous adipose tissue. After three passages, ADSCs were seeded on temperature-responsive culture dishes and collected as cell sheets. ADSC sheets were gently transplanted on the anastomotic site. We evaluated specimens by PKH26GL labeling, macroscopic changes, infiltration of inflammatory cells, and collagen content. Results: Labeled ADSCs remained around the bile duct wall. In the no-ADSC group, more adhesion developed at the hepatic hilum as observed during relaparotomy. Histopathological examination showed that the diameter and cross-sectional area of the bile duct wall were decreased in the ADSC group. In the no-ADSC group, a large number of inflammatory cells and more collagen fibers were identified in the bile duct wall. Conclusions: The present study demonstrated that autologous ADSC sheet transplantation reduced hypertrophic changes in the bile duct wall at the anastomotic site. A long-term follow-up is required to evaluate the efficacy of this mechanism in prevention of biliary anastomotic strictures.

Summary: Background: The aim of this study was to investigate the impact of Daikenchuto (DKT) on early postoperative outcomes after living donor liver transplantation (LDLT), focusing on the prevention of abdominal distension and bacterial translocation. Methods: Adult LDLT recipients were prospectively divided into 2 groups, who were administered DKT (n = 20, group A) or not (n = 20, group B). The area of bowel gas defined as gas volume score (GVS) 7 days after LDLT was calculated. Postoperative liver function tests, the development of bacterial, viral, and fungal infections, and GVS after LDLT were reviewed. Results: There were no significant differences in liver function tests and ammonia level after LDLT. Also, the rates of infection and the result of culture study were not different between groups. The median GVS 7 days after LDLT was not significantly different between groups A (0.26 (range, 0.12–0.58)) and B (0.23 (range, 0.15–0.42)). Conclusions: No positive impact was observed for 14-day DKT administration after LDLT, in terms of preventing infection or abdominal distension. Keywords: Living donor, Liver transplantation, Daikenchuto, Herbal drug, Bowel gas

Objective/Background: Huge aneurysm of the visceral artery is rare and a treatment strategy for such cases has not yet been established. Here, we report a case of huge aneurysm of the common hepatic artery (44-mm diameter) successfully treated by stent placement.Methods: A 77-year-old female patient was referred to our department due to growth of the common hepatic artery aneurysm. The cause of the aneurysm was suspected to be segmental arterial mediolysis. Due to the possibility of a spontaneous rupture, we decided to stent the common hepatic artery.Result: We had some difficulties during the procedure, such as thrombosis of the stent, and it was necessary to insert an additional stent. The procedure was effective and the patient has been doing well without any complications at the 6-year follow-up.Conclusion: Stenting is possible and effective in cases of huge aneurysm of the common hepatic artery. Keywords: Segmental arterial mediolysis, Stenting, Aneurysm

Background: Simultaneous pancreas-kidney transplantation (SPK) is an established therapy for diabetes mellitus (DM) patients with associated end stage renal disease. We report the initial results of SPK in our institution after qualification as transplantation program. Patients and methods: Between September 2017 and July 2018, we performed 3 SPK in type 1 diabetic patients with end-stage renal disease. All grafts were procured from brain-dead marginal donors according Pittsburg criteria. Results: The recipients were 2 men and 1 woman with a mean age of 43 ± 5.4 years. Mean time from DM diagnosis and time on dialysis were 25.7 ± 3.9 years and 19.7 ± 9.1 months. The mean age and HbA1C value of donor were 56.7 ± 0.5 years and 5.67 ± 0.05%. The pancreatic grafts were transplanted intraperitoneally in the right iliac fossa. Two patients required a relaparotomy due to arterial anastomotic hemorrhage and two patients developed acute cellular rejection. With a median follow-up of 13 (6–15) months, patient's and graft's survival rate were 100%. All patients showed HbA1C within normal range, but oral glucose tolerance test showed DM pattern in two patients at 3 months after transplantation. Conclusions: In our initial experience with SPK, mid-term grafts and patient survival appear comparable to the results reported in literature. Despite the limited availability of donors and the use of grafts from marginal donors, a quality pancreas transplantation program can be established even in a small-volume centers. Nonetheless further improvement in surgical techniques and meticulous management appear mandatory. Keywords: Simultaneous pancreas-kidney transplantation, Initial experience, Postoperative bleeding, Acute cellular rejection