Modulation of inflammation and innate immune responses subsequent to endothelial cell damage in lung allo and xenotransplantation
| Project/Area Number |
16H05432
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory surgery
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| Research Institution | Kagoshima University |
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Principal Investigator |
SAHARA Hisashi 鹿児島大学, 総合科学域総合研究学系, 准教授 (90452333)
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| Co-Investigator(Kenkyū-buntansha) |
山田 和彦 鹿児島大学, 総合科学域総合研究学系, 教授 (40241103)
清水 章 日本医科大学, 大学院医学研究科, 大学院教授 (00256942)
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| Research Collaborator |
SEKIJIMA mitsuhiro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | 移植・再生医療 / 肺移植 / 異種移植 / 自然免疫 / 一酸化炭素 / ミニブタ / 霊長類 / CD47 / 異種肺移植 / マクロファージ / 前臨床研究 / アデノシンA2A受容体 / 免疫寛容 / 前臨床実験 / 外科 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
In this translational research using swine and non-human primate (NHP), we established the new strategy to improve the results of both allo and xeno lung transplantation (LTx) especially focused on the protection of endothelium and reducing inflammatory damage following LTx. In Study 1, we showed that A2AR agonist has beneficial effects on pulmonary allograft survival using MHC-defined CLAWN miniature swine. In Study 2, we showed the perioperative inhalation of low-dose carbon monoxide (CO) has beneficial effects on porcine lung xenografts in NHP. Histology showed less inflammatory cell infiltrates, intravascular thrombi, and hemorrhage in the CO-treated animal. In Study 3 using pig-to-NHP xeno-lung transplantation, histologically viable porcine lung grafts beyond 7 days in baboons were achieved. hCD47 expression of donor lungs was detected in both alveoli and vessels only in the 3 grafts surviving >7, 9, and 10 days.
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| Academic Significance and Societal Importance of the Research Achievements |
今回実施した大動物実験は、同種肺移植から異種肺移植への計画的かつ戦略的な研究展開によって、急性期のみならず移植臓器の長期成績までをも評価する研究体制のもとで実施したものである。かつ今回の研究成果は、肺移植だけでなく、他の臓器移植に応用が可能である。臨床移植医療の問題解決として、ドナー適応拡大や移植長期成績の向上、新たな免疫抑制療法による負担を強いることのない免疫寛容誘導までをも見据えた有力な新規治療戦略の確立という点において、学術面のみならず社会的意義の高い成果であると考える。
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Report
(4 results)
Research Products
(16 results)
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[Presentation] Histologically proven survival of porcine lung xenografts in baboons for up to 10 days using double transgenic hCD47/hCD55 GalT-KO donors2017
Author(s)
Watanabe H, Sahara H, Nomura S, Tanabe T, Doi R, Ekanayake-Alper D, Boyd L, Danton M, Arn J, Hawley J, Shimizu A, Lorber M, Sykes M, Sachs D, Yamada K
Organizer
14th Congress IXA (International Xenotransplantation Association 2017)
Related Report
Int'l Joint Research
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