1 Department of Surgery; Graduate School of Medicine; Kyoto University; Kyoto, Japan (Ohe, Nafady-Hego, Uemoto, Koshiba) 2 Department of Experimental Pathology; Institute for Frontier Medical Science; Kyoto University; Kyoto, Japan (Li, Sakaguchi) 3 Department of Ubiquitous Health Informatics; Graduate school of Medicine; The University of Tokyo; Tokyo, Japan (Kayo) 4 Transplantation Research Immunology Group; Nuffield Department of Surgery; University of Oxford; John Radcliffe Hospital; Headington, Oxford, United Kingdom (Wood) 5 Department of Surgery & Medicine; University of Cambridge; United Kingdom and National University of Singapore, Singapore (Calne).
[Show abstract][Hide abstract] ABSTRACT: Along with the increasing need for living-donor liver transplantation (LDLT), the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts) of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH). The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038), demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001). Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.
PLoS ONE 04/2014; 9(4):e93749. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: T-cell receptor Vδ2 γδ T cells (Vδ2 cells) participate in host defense, whereas Vδ1 γδ T cells (Vδ1 cells) may regulate immune responses. Vδ1 cells appear to play a role in fetomaternal tolerance and our aim was to examine their role in liver transplant tolerance. METHODS: To determine whether Vδ1 cells increase within accepted grafts after semiallogeneic pediatric liver transplantation, the Vδ1/Vδ2 ratio was assessed at the transcriptional level and the complementarity-determining region 3 loop of the δ chain of Vδ1 cells was sequenced in biopsies from immunosuppression-free (n=6) or almost free (n=3) liver transplant recipients, referred to as group tolerance (Gr-Tol; n=9). The results were compared with biopsies from grafts of recipients on maintenance immunosuppression due to concern of rejection (Gr-IS; n=11). Chronically rejected grafts (Gr-CR; n=6) and normal livers (Gr-NL; n=8) were also examined. RESULTS: The Vδ1/Vδ2 ratio was the highest in Gr-Tol (0.07±0.06) compared with Gr-IS (0.03±0.02; P=0.04), Gr-CR (0.01±0.02; P=0.008), and Gr-NL (0.02±0.04; P=0.01). There was an identical complementarity-determining region 3 sequence (100% homologous) among all recipients in Gr-Tol, which was dominant in six of nine recipients. This sequence was not seen in Gr-IS or Gr-CR, although it was observed in five of six normal livers. CONCLUSIONS: A unique Vδ1-bearing T-cell clone accumulates within accepted human liver grafts. It might be useful as a biomarker of tolerance and the identification of its ligand might aid in the development of a novel strategy for tolerance induction.
[Show abstract][Hide abstract] ABSTRACT: Transplanting a uterus has unique characteristics, since a successful outcome is represented only by the birth of a viable healthy child. For this reason, critical issues in this type of transplantation differ profoundly from those of other solid organs and, beside a functioning uterus, involve 3 additional steps. First, at the time of implantation, the quality of embryo is tested by specialized decidual cells surrounding the implanting embryo; such testing is aimed at allowing the development of a normal embryo. Second, from early gestation onward, blood supply to the uterus increases from 45 to 750mL per minute. Vascular anastomoses should support such a marked increase in blood flow. Third, full transformation of spiral arterioles in the placental bed is required to direct 75% of the uterine blood flow to the intervillous space. Unfortunately, no suitable animal model is available for experimentation. Three overarching ethical issues must be considered. Should organ transplant be conducted when it is not absolutely necessary as a life-saving or quality-of-life-saving measure? To what extent should medicine delimit its potential in spite of societal desires? Should society demand from medicine the application of whichever technology can be developed and, if so, to what extent?
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 07/2013; · 1.41 Impact Factor
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