Attenuation of hyperacute dysfunction and coagulopathy in GalT-KO pulmonary xenotransplantation
| Project/Area Number |
23390337
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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 |
Thoracic surgery
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| Research Institution | Kagoshima University |
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Principal Investigator |
SAHARA Hisashi 鹿児島大学, 医用ミニブタ・先端医療開発研究センター, 准教授 (90452333)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Kazuhiko 鹿児島大学, 医用ミニブタ・先端医療開発研究センター, 教授 (40241103)
NAGASHIMA Hiroshi 明治大学, 農学部, 教授 (50318664)
DATE Hiroshi 京都大学, 医学(系)研究科(研究院), 教授 (60252962)
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| Co-Investigator(Renkei-kenkyūsha) |
SHIMIZU Akira 日本医科大学, 医学部, 教授 (00256942)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2011: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | トランスレーショナルリサーチ / 異種肺移植 / GalT-KOブタ / カニクイザル / 一酸化炭素 / 急性期肺機能不全 / 移植・再生医療 / Ex-vivo灌流 / CalT-KOブタ / 血小板 / 肺血管抵抗 |
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| Research Abstract |
The results of both heart and kidney GalT-KO swine-to-primate studies have been more encouraging than for lung xenotransplantation. This may be because research in pulmonary xenotransplantation is limited. Here, we evaluated 1) whether GalT-KO lungs could prevent hyper-acute pulmonary xenograft dysfunction using ex-vivo lung perfusion or in-vivo orthotopic left lung transplant model and 2) the effect of carbon monoxide (CO) on reducing the development of microangiopathy (CO-treated animals). GalT-KO lungs exhibited stable pulmonary function compared with wild-type lungs when perfused with human blood in an ex-vivo perfusion model, which was confirmed by the in-vivo transplant model. Although, thrombotic microangiopathy ultimately developed in all grafts of the CO-treated animals, the degree of microangiopathy was reduced in these animals. Reduction of the innate immune response by CO treatment would be one of the therapeutic strategies for prolonging pulmonary xenograft survival.
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Production of cloned NIBS (Nippon Institute for Biological Science) and α-1, 3-galactosyltransferase knockout MGH miniature pigs by somatic cell nuclear transfer using the NIBS breed as surrogates2013
Author(s)
Shimatsu Y, Yamada K, Horii W, Hirakata A, Sakamoto Y, Waki S, Sano J, Saitoh T, Sahara H, Shimizu A, Yazawa H, Sachs DH, Nunoya T
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Journal Title
Xenotransplantation
Volume: 20(3)
Issue: 3
Pages: 157-64
DOI
Related Report
Peer Reviewed
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[Journal Article] Autoimmune sensitization to cardiac myosin leads to acute rejection of cardiac allografts in miniature swine2011
Author(s)
Veillette GR, Sahara H, Meltzer AJ, Weiss MJ, Iwamoto y Kim KM, Rosengard BR, Allan JS, Houser SL, Sachs DH, Benichou G, Madsen JC
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Journal Title
Transplantation
Volume: 91(11)
Issue: 11
Pages: 1187-1191
DOI
Related Report
Peer Reviewed
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[Presentation] Attenuation of hyperacute dysfunction and microangiopathy by the treatment of carbon monoxide in GalT-KO pulmonary xenotransplantation2013
Author(s)
Sahara H, Nagashima H, Miura K, Waki S, Kawai A, Nakano K, Matsunari H, Arai Y, Sekijima M, Tasaki M, Setoyama K, Shimizu A, Date H, Yamada K
Organizer
12th Congress IXA (International Xenotransplantation Association 2013)
Place of Presentation
Osaka
Related Report
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[Presentation] Attenuation of hyperacute dysfunction and coagulopathy in GalT-KO pulmonary xenotransplantation2013
Author(s)
Sahara H, Nagashima H, Sekijima M, Tasaki M, Setoyama K, Matsunari H, Nakano K, Date H, Shimizu A, Yamada K
Organizer
The 13th Congress of the Asian Society of Transplantation
Place of Presentation
Kyoto, Japan
Related Report
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[Presentation] Carbon monoxide administered only to the donor is sufficient to prolong pulmonary allograft survival across a fully MHC-mismatched barrier in CLAWN miniature swine.2012
Author(s)
Sahara H, Sekijima M, Tasaki M, Oku M, Nishimura H, Iwanaga T, Iwanaga T, Sekijima A, Setoyama K, Shimizu A, Yamada K
Organizer
24th International Congress of the Transplantation Society
Place of Presentation
Berlin
Related Report
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[Presentation] Prevention of hyper-acute pulmonary xenograft dysfunction using GalT-KO swine in an ex-vivo lung perfusion model2011
Author(s)
Sahara H, Nagashima H, Sekijima M, Tasaki M, Setoyama K, Matsunari H, Nakano K, Date H, Shimizu A, Yamada K
Organizer
CTS (Cell Transplant Society) -IXA (International Xenotransplantation Association) 2011 Joint Congress
Place of Presentation
Miami beach, FL, US
Related Report
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