Recipient hepatectomy with inferior vena cava (IVC) preservation, the piggy back (PGB) technique, was adopted as our routine option in the management of the anhepatic phase of orthotopic liver transplantation (OLT) to avoid the use of veno-venous bypass (VV-BP). In the last 5 years, 119 OLT in adult patients have been performed in our unit. In the first period (47 OLT), VV-BP was used in 59% of the cases and cross-clamping in the rest. In the second period, following the introduction of the PGB technique, 72 OLT were performed. VV-BP was used in 5.5% of the cases, PGB technique in 87.5% and cross-clamping in 6.9%. There was a significant reduction in the need for VV-BP in the second period. Operating time and blood transfusion were significantly greater in the VV-BP group. No PGB technique related complications were observed. In conclusion, the PGB technique reduced the need for VVBP with consequent savings in time, blood transfusion and the cost of OLT.

Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (iPSC-RPE) cells in patients with age-related macular degeneration. However, there was an issue regarding immune rejection after transplantation. In this study, we established a preoperational in vitro “drug–lymphocytes–grafts immune reaction (Drug-LGIR)” test to determine the medication for immune rejection using host immunocompetent cells (lymphocytes) and transplant cells (target iPSC-RPE cells) together with different medications. The adequacy of the test was assessed by in vivo transplantation in monkey models together with medication based on in vitro data. In the results of Drug-LGIR tests, some drugs exhibited significant suppression of RPE cell-related allogeneic reactions, while other drugs did not, and the efficacy of each drug differed among the recipient monkeys. Based on the results of Drug-LGIR, we applied cyclosporine A or local steroid (triamcinolone) therapy to two monkeys, and successfully suppressed RPE-related immune rejections with RPE grafts, which survived without any signs of rejection under drug administration. We propose that our new preoperational in vitro Drug-LGIR test, which specifies the most efficacious medication for each recipient, is useful for controlling immune attacks with personalized treatment for each patient after retinal transplantation.

Eighty-four adult patients were recruited from four centres in Spain to evaluate the efficacy and safety of low-dose (0.1 mg/kg per day) oral tacrolimus plus corticosteroid immunosuppression in liver transplantation. The median daily dose of tacrolimus was increased during the first 3 weeks of therapy from an initial dose of 0.1 mg/kg per day to a maximum of 0.145 mg/kg per day and was subsequently decreased gradually to a minimum of 0.076 mg/kg per day at 1 year. At 7 days posttransplantation, 87.7% of patients had trough whole blood levels of tacrolimus within the therapeutic range (5-20 ng/ml), and the median levels remained fairly constant during the rest of the year (10.1-11.8 ng/ml). None of the patients required intravenous administration of tacrolimus. At 1 year, Kaplan-Meier estimates showed that 73.8% of the patients were receiving tacrolimus monotherapy without the need for corticosteroids. One-year patient and graft survival were 75.9% and 72.3%, respectively. The incidence of acute rejection was 51.2%; 9.5% of cases resolved spontaneously without antirejection therapy and 10.7% were corticosteroid resistant. Only 1 patient (1.2%) developed chronic rejection. The most important adverse events were hypertension (45.2%), tremor (44.0%), diabetes mellitus (33.3%), diarrhoea (31%) and nephrotoxicity (29.8%). Severe neurotoxicity-like convulsions (4.8%), dysarthria (9.5%), delirium (1.2%), coma (1.2%) and the need for haemodialysis (3 patients) were uncommon. In conclusion, low-dose oral tacrolimus immunosuppression is associated with low toxicity without compromising efficacy.

Eighty-four adult patients were recruited from four centres in Spain to evaluate the efficacy and safety of low-dose (0.1 mg/kg per day) oral tacrolimus plus corticosteroid immunosuppression in liver transplantation. The median daily dose of tacrolimus was increased during the first 3 weeks of therapy from an initial dose of 0.1 mg/kg per day to a maximum of 0.145 mg/kg per day and was subsequently decreased gradually to a minimum of 0.076 mgikg per day at 1 year. At 7 days posttransplantation, 87.7 % of patients had trough whole blood levels of tacrolimus within the therapeutic range (5-20 ng/ml), and the median levels remained fairly constant during the rest of the year (10.1-1 1.8 ng/ml). None of the patients required intravenous administration of tacrolimus. At 1 year, Kaplan-Meier estimates showed that 73.8 % of the patients were receiving tacrolimus monotherapy without the need for corticosteroids. Oneyear patient and graft survival were 75.9 % and 72.3 YO, respectively. The incidence of acute rejection was 51.2 %: 9.5 % of cases resolved spontaneously without antirejection therapy and 10.7 % were corticosteroid resistant. Only 1 patient ( 1.2 % ) developed chronic rejection. The most important adverse events were hypertension (45.7 % ), tremor (44.0%), diabetes mellitus ( 3 3 . 3 % ) diarrhoea (31 % ) and nephrotoxicity (29.8 % ). Severe neurotoxicity-like convulsions (4.8 %), dysarthria (9.5 % ), delirium (1 .2 % ), coma (1.2 % ) and the need for haemodialysis (3 patients) were uncommon. In conclusion, low-dose oral tacrolimus immunosuppression is associated with low toxicity without compromising efficacy.

Retinal ganglion cells (RGCs) are impaired in patients such as those with glaucoma and optic neuritis, resulting in permanent vision loss. To restore visual function, development of RGC transplantation therapy is now underway. Induced pluripotent stem cells (iPSCs) are an important source of RGCs for human allogeneic transplantation. We therefore analyzed the immunological characteristics of iPSC-derived RGCs (iPSC-RGCs) to evaluate the possibility of rejection after RGC transplantation. We first assessed the expression of human leukocyte antigen (HLA) molecules on iPSC-RGCs using immunostaining, and then evaluated the effects of iPSC-RGCs to activate lymphocytes using the mixed lymphocyte reaction (MLR) and iPSC-RGC co-cultures. We observed low expression of HLA class I and no expression of HLA class II molecules on iPSC-RGCs. We also found that iPSC-RGCs strongly suppressed various inflammatory immune cells including activated T-cells in the MLR assay and that transforming growth factor-β2 produced by iPSC-RGCs played a critical role in suppression of inflammatory cells in vitro. Our data suggest that iPSC-RGCs have low immunogenicity, and immunosuppressive capacity on lymphocytes. Our study will contribute to predicting immune attacks after RGC transplantation.