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Q-FISH Measurement of Hepatocyte Telomere Lengths in Donor Liver and Graft after Pediatric Living-Donor Liver Transplantation: Donor Age Affects Telomere Length Sustainability

机译:Q-FISH测量小儿活体-供体肝移植后供肝和移植物中肝细胞端粒的长度:供体年龄影响端粒长度的可持续性

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摘要

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.
机译:随着对活体供肝移植(LDLT)的需求不断增加,器官短缺问题已成为一个严重的问题。因此,来自老年供体的器官的使用一直在增加。尽管LDLT的短期结果已大大改善,但影响移植患者长期结果的问题仍未解决。此外,由于已经报道了有关供体年龄与LT / LDLT结果之间关系的矛盾数据,因此关于长期供体是否影响LT / LDLT后移植物的长期结果的问题仍未解决。为了探讨肝细胞端粒长度是否反映了LDLT的结局,我们分析了成年LDLT患儿至成人LDLT后超过5年的12个成对小儿LDLT供体和受体(移植物)的资料丰富的活检样本中肝细胞的端粒长度闭锁,使用定量荧光原位杂交(Q-FISH)。配对样品中的端粒长度显示出供体和移植肝细胞之间的牢固关系(r = 0.765,p = 0.0038),证明了我们的Q-FISH方法用于细胞特异性评估的可行性。虽然8对对在供体和受体的端粒长度之间没有显着差异,但其他4对对在受体中的端粒明显短于供体。多元回归分析显示,后一组的供体比前一组大(p = 0.001)。尽管受试者人数很少,但这项初步研究表明,供体的年龄是影响小儿LDLT后肝细胞端粒长度可持续性的关键因素,并且如果对移植物进行免疫学上的良好控制,则移植肝中的端粒可能会延长更长的时间。

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