2018 Fiscal Year Final Research Report

Modulation of inflammation and innate immune responses subsequent to endothelial cell damage in lung allo and xenotransplantation

Research Project

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Project/Area Number	16H05432
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Respiratory surgery
Research Institution	Kagoshima University
Principal Investigator	SAHARA Hisashi 鹿児島大学, 総合科学域総合研究学系, 准教授 (90452333)
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)
Research Collaborator	SEKIJIMA mitsuhiro
Project Period (FY)	2016-04-01 – 2019-03-31
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
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.
Free Research Field	呼吸器外科学
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。