title: Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.
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.
authors.affiliation: Department of Surgery, Nippon Medical School, Tokyo, Japan; Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Kawano
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Ishikawa
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Aida
authors.affiliation: Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Sanada
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Izumiyama-Shimomura
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
authors.forename: Steven S S
authors.initials: SS
authors.lastname: Poon
authors.affiliation: Department of Clinical Pathology, Ebina General Hospital, Kanagawa, Japan.
authors.forename: Koshi
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Mizuta
authors.affiliation: Department of Surgery, Nippon Medical School, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Uchida
authors.affiliation: Department of Surgery, Nippon Medical School, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tajiri
authors.affiliation: Department of Transplant Surgery, Jichi Medical University, Tochigi, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kawarasaki
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Kaiyo
authors.initials: K
authors.lastname: Takubo
mesh_terms: D000328:Adult; D000367:Age Factors; D002648:Child; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007223:Infant; D016031:Liver Transplantation / Q000009:adverse effects*; D019520:Living Donors; D008297:Male; D016615:Telomere / Q000235:genetics*
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