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Muscle-targeted transfer of plasmid DNA for suppression of chronic rejection after lung transplantation

Research Project

Project/Area Number 12671300
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionNiigata University

Principal Investigator

TSUCHIDA Masanori  Medical Hospital, Niigata University, Lecturer, 医学部・附属病院, 講師 (60293221)

Co-Investigator(Kenkyū-buntansha) AOKI Tadashi  Medical Hospital, Niigata University, Assistant, 医学部・附属病院, 助手 (20334659)
平原 浩幸  新潟大学, 医学部・附属病院, 助手 (00303157)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
KeywordsGene transfer / Electroporation / IL-10 / Tracheal transplantation / 閉塞性細気管支炎
Research Abstract

Long-term survival after lung transplantation is limited mainly by bronchiolitis obliterans, which is regarded as a form of chronic rejection. To examine whether anti-inflammatory cytokine prevents chronic rejection, we transferred mouse and viral IL-10 to the recipient animals that were transplanted with tracheal allografts. Naked plasmid DNA containing mouse or viral IL-10 was transferred to the animal by intramuscular injection followed by electroporation. After intramuscular injection, the serum levels of IL-10 and the duration of cytokine expression were examined. After 72 hours, IL-10 level reached peak and could be detected until 2 weeks. We next examined preventive effects of IL-10 on chronic rejection. Histology and degree of luminal obliteration of the trachea were studied in the animals with or without expression ofIL-10. Although there are several animals that have improved luminal obliteration, the preventive effects varied among animals. To maintain the level of IL-10 high for 4 weeks, genes were transferred 4 times after tracheal transplantation. However, consistent improvement was not obtained. Although there may be possibility of prevention of bronciotitis obliterans by inducing IL-10 in vivo, it's effect was not consistent and combination therapy with other cytokines should be considered.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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