Citrin-deficient patient-derived induced pluripotent stem cells as a pathological liver model for congenital urea cycle disorders.

Citrin deficiency is a congenital secondary urea cycle disorder lacking useful disease models for effective treatment development. In this study, human induced pluripotent stem cells (iPSCs) were generated from two patients with citrin deficiency and differentiated into hepatocyte-like cells (HLCs). Citrin-deficient HLCs produced albumin and liver-specific markers but completely lacked citrin protein and expressed argininosuccinate synthase only weakly.

Efficient protocol for the differentiation of kidney podocytes from induced pluripotent stem cells, involving the inhibition of mTOR.

The mechanistic/mammalian target of rapamycin (mTOR) is involved in a wide range of cellular processes. However, the role of mTOR in podocytes remains unclear. In this study, we aimed to clarify the role of mTOR in podocyte differentiation from human induced pluripotent stem cells (hiPSCs) and to establish an efficient differentiation protocol for human podocytes.

The Induction of Parathyroid Cell Differentiation from Human Induced Pluripotent Stem Cells Promoted Via TGF-α/EGFR Signaling.

The parathyroid gland plays an essential role in mineral and bone metabolism. Cultivation of physiological human parathyroid cells has yet to be established and the method by which parathyroid cells differentiate from pluripotent stem cells remains uncertain. Therefore, it has been hard to clarify the mechanisms underlying the onset of parathyroid disorders, such as hyperparathyroidism.

A multiple-funnels cell culture insert for the scale-up production of uniform cell spheroids.

Introduction: Formation of cell spheres is an important procedure in biomedical research. A large number of high-quality cell spheres of uniform size and shape are required for basic studies and therapeutic applications. Conventional approaches, including the hanging drop method and suspension culture, are used for cell sphere production.

Effects of Activin in Embryoid Bodies Expressing Fibroblast Growth Factor 5.

Nodal/activin signaling is indispensable for embryonic development. We examined what activin does to the embryoid bodies (EBs) produced from mouse embryonic stem cells (mESCs) expressing an epiblast marker. The EBs were produced by culturing mESCs by the hanging drop method for 24 hours.

Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.

Islet transplantation is a minimally invasive treatment for severe diabetes. However, it often requires multiple donors to accomplish insulin-independence and the long-term results are not yet satisfying. Therefore, novel ways to overcome these problems have been explored.

Immunoisolation effect of polyvinyl alcohol (PVA) macroencapsulated islets in type 1 diabetes therapy.

Islet transplantation has shown great success in the treatment of type 1 diabetes since the Edmonton protocol was established. However, it still has two major problems to overcome: the lack of organ donors and the side effects of immunosuppression. Encapsulated islets have emerged as a potential option for islet transplantation because it can, at least partly, overcome these two problems.

Difficulty in sustaining hepatic outflow in left lobe but not right lobe living donor liver transplantation.

Background: Hepatic outflow block is one of the major complications leading to severe graft dysfunction after left lobe living donor liver transplantation (LDLT).

Methods: Medical records of 46 recipients of a left lobe LDLT were reviewed. The method of outflow reconstruction and post-transplant morphological changes of hepatic veins were investigated.

Reduction of left-lateral segment from living donors for liver transplantation in infants weighing less than 7 kg: technical aspects and outcome.

LLS reduction has been frequently used in infants weighing <7 kg. Twenty recipients weighing <7 kg at the time of LDLT, median age 11.0 months and body weight 5.

The in vivo performance of polyvinyl alcohol macro-encapsulated islets.

Islet transplantation is a method for the treatment of type 1 diabetes mellitus (DM) and has been widely performed around the world. The long-term cryopreservation of islets shows many advantages in the field of islet transplantation. Previous studies have described the development of sheet-type polyvinyl alcohol (PVA) macro-encapsulated islets (MEI) to treat type 1 DM without any immunotherapy.

Massive ascites after living donor liver transplantation with a right lobe graft larger than 0.8% of the recipient's body weight.

Background: There are only limited data on post-transplant ascites unrelated to small-sized grafts in living donor liver transplantation (LDLT).

Methods: The subjects were 59 adult patients who had received right lobe LDLT with a graft weight-to-recipient weight ratio (GRWR)>0.8%.

Gastric volvulus as a complication in the recipients after adult living donor liver transplantation.

Background: We report 4 adult cases of mesenteroaxial gastric volvulus after living donor liver transplantation (LDLT).

Results: All 4 recipients were female with a median age of 31 years (range, 21-69). All had undergone right lobe LDLT.

How to handle a huge portosystemic shunt in adult living donor liver transplantation with a small-for-size graft: report of a case.

Little attention has been paid to a ligation of the spontaneous portosystemic shunt in adult living donor liver transplantation (LDLT). A 33-year-old Japanese man with cryptogenic liver cirrhosis accompanied by a huge splenorenal shunt underwent LDLT. Acute cellular rejection produced "to and fro" portal venous flow on postoperative day (POD) 10.

Rapamycin inhibits proliferation and migration of hepatoma cells in vitro.

Background: Systemic immunosuppression represents the major factor for cancer recurrence after orthotopic liver transplantation for hepatocellular carcinoma (HCC). Rapamycin is an immunosuppressant with unique antitumoral properties. Although rapamycin has been successfully used in HCC patients after liver transplantation, the detailed mechanisms of rapamycin action on tumor cells are poorly understood.

Revisited impact of recipient age on the outcome of living donor liver transplantation for biliary atresia in the recent "transplantation era" in Japan.

To re-evaluate the impact of recipient age on the outcome of LDLT for BA in an era in which LDLT is the established treatment for BA in Japan. Thirty-one patients with BA who underwent LDLT were divided into four groups regarding the age at LDLT: infants <1 yr old (group A; n = 14); young children 1 to 6 yr old (group B; n = 8); school children 6 to 15 yr old (group B; n = 5); and adults > or =15 yr old (group D; n = 4). Pre-, peri-, and postoperative factors were compared among the four groups.

Biliary reconstruction for infantile living donor liver transplantation: Roux-en-Y hepaticojejunostomy or duct-to-duct choledochocholedochostomy?

Hepaticojejunostomy is a standard biliary reconstruction method for infantile living donor liver transplantation (LDLT), but choledochocholedochostomy for infants is not generally accepted yet. Ten pediatric recipients weighing no more than 10 kg underwent duct-to-duct choledochocholedochostomy (DD) for biliary reconstruction for LDLT. Patients were followed up for a median period of 26.

Vascular reconstruction and complications in living donor liver transplantation in infants weighing less than 6 kilograms: the Kyoto experience.

Smaller-size infants undergoing living-donor liver transplantation (LDLT) are at increased risks of vascular complications because of their smaller vascular structures in addition to vascular pedicles of insufficient length for reconstruction. Out of 585 child patients transplanted between June 1990 and March 2005, 64 (10%) weighing less than 6 kg underwent 65 LDLTs. Median age and weight were 6.

Development of pulmonary hypertension in 5 patients after pediatric living-donor liver transplantation: de novo or secondary?

The development of portopulmonary hypertension (PH) in a patient with end-stage liver disease is related to high cardiac output and hyperdynamic circulation. However, PH following liver transplantation is not fully understood. Of 617 pediatric patients receiving transplants between June 1990 and March 2004, 5 (median age 12 yr, median weight 24.

Cold preservation of islets in UW solution--with special reference to apoptosis.

Background: Apoptosis progresses in cultured islets. Little is known with regard to apoptosis under cold preservation. We examined viability and function of islets in University of Wisconsin (UW) solution.

Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University.

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years.

The fungal DNA examination is useful as a sensitive parameter for the initiation and the quit of antifungal therapy in immunocompromised pediatric patients after surgery.

The purpose of this study is whether the fungal deoxyribonucleic acid (DNA) examination is useful as a sensitive parameter for pediatric surgical patients with mycosis. The eleven episodes of five cases (4 cases; progressive liver disease after biliary atresia operation, 1 case; short bowel syndrome and long term total parenteral nutrition with megacystis microcolon intestinal hypoperistalsis syndrome) with mycosis were divided into two groups according to the difference of therapeutic protocols. The sensitivity of fungal DNA examination, serum Candida antigen level, plasma beta-D glucan level, and blood culture were evaluated at the onset of infection and at the quit of antifungal medication under the protocols respectively.

PVA hydrogel sheet macroencapsulation for the bioartificial pancreas.

We newly developed a sheet-type macroencapsulation device entrapping rat islets from 3% polyvinyl alcohol (PVA) dissolved in Euro-Collins solution containing 10% fetal bovine serum and 5% dimethyl sulfoxide (PVA + EC) using a freezing/thawing technique. The same encapsulation technique but with 3% PVA dissolved only in double-distilled water (PVA) and a culture of free islets were served as controls. After 14-day culture in the CMRL-1066 medium, the islet recovery rate, morphological changes, insulin content, and insulin secretion were evaluated in vitro to prove the feasibility of this method of encapsulation.

Inhibition of acute rejection after skin or cardiac transplantation by administration of donor antigens in the rat.

Purpose: We examined differences in host immunologic changes induced by the intravenous or intraportal administration of donor antigens at engrafting and evaluated their contribution to graft survival using a rat transplantation model.

Methods: Lewis rat recipients were given either an intravenous or intraportal injection of donor splenocytes (1 x 10(8)) immediately after receiving skin grafts from Brown Norway donors. The immunologic responses were analyzed by mixed lymphocyte reaction (MLR) and profiles of interferon-Gamma, interleukin (IL)-2, and IL-10 in MLR supernatants.