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

被引:11
作者
Kawano, Youichi [1 ,2 ]
Ishikawa, Naoshi [2 ]
Aida, Junko [2 ]
Sanada, Yukihiro [3 ]
Izumiyama-Shimomura, Naotaka [2 ]
Nakamura, Ken-ichi [2 ]
Poon, Steven S. S. [4 ]
Matsumoto, Koshi [5 ]
Mizuta, Koichi [3 ]
Uchida, Eiji [1 ]
Tajiri, Takashi [1 ]
Kawarasaki, Hideo [3 ]
Takubo, Kaiyo [2 ]
机构
[1] Nippon Med Sch, Dept Surg, Tokyo 113, Japan
[2] Tokyo Metropolitan Inst Gerontol, Res Team Geriatr Pathol, Tokyo, Japan
[3] Jichi Med Univ, Dept Transplant Surg, Shimotsuke, Tochigi, Japan
[4] British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[5] Ebina Gen Hosp, Dept Clin Pathol, Ebina, Kanagawa, Japan
来源
PLOS ONE | 2014年 / 9卷 / 04期
基金
日本学术振兴会;
关键词
IN-SITU HYBRIDIZATION; REPLICATIVE SENESCENCE; CHROMOSOMAL INSTABILITY; CELLULAR SENESCENCE; LINGUAL EPITHELIUM; HUMAN FIBROBLASTS; ALLOGRAFTS; OUTCOMES; CELLS; LIFE;
D O I
10.1371/journal.pone.0093749
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
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.
引用
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页数:10
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