The development for the stable high expression of numerous transgenes.
Project/Area Number |
16H05401
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General surgery
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Research Institution | Osaka University |
Principal Investigator |
Miyagawa Shuji 大阪大学, 医学系研究科, 准教授 (90273648)
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Co-Investigator(Kenkyū-buntansha) |
長嶋 比呂志 明治大学, 農学部, 専任教授 (50318664)
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Research Collaborator |
Ikawa Masahito
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | special construct / pig ROSA26 locus / CD200 / CL-SP-D / CD31 / PQA-18 / Xenotransplantation / Gene-modified pigs / Hybrid gene / Complement / Macrophage / Innate Immunity / バイオ人工膵島 / 異種移植 / 新奇遺伝子開発 / 補体制御因子 / Hybrid / Hybid / 抗凝固因子 / バイオテクノロジー / 移植・再生医療 / 生物・生体工学 / 応用動物 / 遺伝子 |
Outline of Final Research Achievements |
We have produced special construct genes. The expression of NCTDM was not efficient, then separated to C1DM & TM. HLA-Ev(147)-2A-beta2m was also produced. In addition, we produced PI-anchored CD47, PI-anchored TFPI. A project of pig ROSA26 locus was started. We demonstrated the targeted knock-in of a gene cassette in this locus. Three guide RNA-sequences were designed, using CRISPR/Cas9 system, and the cleavage efficiency of each plasmid was assessed. We studied novel strategies for suppressing macrophages and neutrophil-mediated xenogeneic rejection using pig ROSA26 locus. Moreover, we focused on the effect of new immunosuppressants on monocyte/macrophages, such as a PQA-18. PQA-18 showed the potential function on macrophage-mediated cytotoxicity, as an immunosuppressant for xenotransplantation.
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Academic Significance and Societal Importance of the Research Achievements |
今回の我々の研究は、国際的にも独自性が高いものであり、遺伝子改変ブタ作りに有効である。また、ROSA26の座に遺伝子をknockinさせる方法を確立させる事も有効である。更に、新たに異種移植に有効な分子を数々検定し、また免疫抑制剤を研究する事も、この分野に非常に有効と考えられる。 我々がこれらの遺伝子改変ブタを作出できなければ、外国の遺伝子改変ブタを使う事になる。これに伴い、関連する分野も含めて日本のこの分野での立ち遅れが必至となる。逆に、成功すれば、アジアを中心に、アメリカ、欧州への輸出が可能になり、これまで人の死を前提としていた移植医療を根本的に変える事になる。
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Human CD31 on porcine cells suppress xenogeneic neutrophil-mediated cytotoxicity via the inhibition of NETosis2018
Author(s)
Han-Tang Wang, Akira Maeda, Rieko Sakai, Pei-Chi Lo, Chihiro Takakura, Patmika Jiaravuthisan, Afifah Mod Shabri, Rei Matsuura, Tasuku Kodama, Shohei Hiwatashi, Hiroshi Eguchi, Hiroomi Okuyama and Shuji Miyagawa
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Journal Title
Xenotransplantation
Volume: 印刷中
Related Report
Peer Reviewed
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[Journal Article] The State of Xenotransplantation2017
Author(s)
Shuji Miyagawa, Akira Maeda, Hiroshi Eguchi, Rieko Sakai, Pei-Chi Lo, Hantang Wang, Chihiro Takakura, Tasuku Komama, Rei Matsuura and Hiroomi Okuyama
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Journal Title
Xenotransplantation - New Insights
Volume: -
Pages: 3-10
DOI
ISBN
9789535133551, 9789535133568
Related Report
Open Access
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[Presentation] Human CD31 suppress macrophage-mediated xenogeneic rejection2018
Author(s)
Akira Maeda, Wang Han-Tang, Chihiro Takakura, Rieko Sakai, Pei-Chi Lo, Rei Matsuura, Tasuku Kodama, Shohei Hiwatashi, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
Organizer
The Transplantation Society
Related Report
Int'l Joint Research
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[Presentation] PQA-18, a novel immunosuppressant, suppresses macrophage differentiation and macrophage-mediated xenogeneic cytotoxicity2018
Author(s)
Pei-Chi Lo, Rieko Sakai, Akira Maeda, Chihiro Takakura, Rei Matsuura, Tasuku Kodama, Shohei Hiwatashi, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
Organizer
The Transplantation Society
Related Report
Int'l Joint Research
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[Presentation] The strategies for preventing the macrophage-mediated rejection in xenotransplantation2018
Author(s)
Akira Maeda, Lo Pei-chi, Rieko Sakai, Yuki Noguchi, Tasuku Kodama, Rei Matsuura, Tomohisa Yoneyama, Chihiro Takakura, Hiroshi Eguchi, Masahito Watanabe, Hiroshi Nagashima, Hiroomi Okuyama, Shuji Miyagawa
Organizer
APITA 2019, Asia Pancreas and islet Transplantation Association
Related Report
Int'l Joint Research / Invited
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[Presentation] PQA-18, a novel immunosuppressant, suppresses macrophage differentiation and macrophage-mediated xenogeneic cytotoxicity2018
Author(s)
Pei-Chi Lo, Akira Maeda, Rieko Sakai, Chihiro Takakura, Rei Matsuura, Tasuku Kodama, Shohei Hiwatashi, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
Organizer
第20回日本異種移植研究会
Related Report
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[Presentation] The innate immunological response of pigs against humans2017
Author(s)
Rieko Sakai, Masahito Watanabe, Akira Maeda, Pei-chi Lo, Han-Tang Wang, Rei Matsuura, Tasuku Kodama, Hiroshi Eguchi, Hitomi Matsunari, Ryo Inoue, Hiroshi Nagashima, Hiroomi Okuyama, Shuji Miyagawa
Organizer
The 14th International Xenotransplantation Association, in Baltimore
Related Report
Int'l Joint Research
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[Presentation] Suppression of macrophage-mediated cytotoxicity by a membrane-type SP-D2017
Author(s)
Patmika Jiaravuthisan, Akira Maeda, Han-Tang Wang, Rieko Sakai, Afifah Mohd Shabri, Rei Matsuura, Tasuku Kodama, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
Organizer
The 14th International Xenotransplantation Association, in Baltimore
Related Report
Int'l Joint Research
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[Presentation] The membrane-type surfactant protein D may provide an effective therapeutic strategy to inhibit macrophage-mediated xenograft rejection2017
Author(s)
Shuji Miyagawa, Patmika Jiaravuthisan, Akira Maeda, Han-Tang Wang, Pei-chi Lo, Rieko Sakai, Afifah Mohd Shabri, Rei Matsuura, Tasuku Kodama, Takehisa Ueno, Hiroshi Eguchi, Hiroomi Okuyama
Organizer
CAST 2017 in Cebu
Related Report
Int'l Joint Research
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[Presentation] The immunological response of pigs anti-human cell, included issues such as the production of natural antibodies in newborn2017
Author(s)
Rieko Sakai, Masahito Watanabe, Akira Maeda, Pei-chi Lo, Han-Tang Wang, Rei Matsuura, Tasuku Kodama, Takehisa Ueno, Hiroshi Eguchi, Hitomi Matsunari, Ryo Inoue, Hiroshi Nagashima, Hiroomi Okuyama, Shuji Miyagawa
Organizer
CAST 2017 in Cebu
Related Report
Int'l Joint Research
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[Presentation] CD200 suppresses the M0 but not M1 macrophage mediated xenocytotoxicity2017
Author(s)
Rieko Sakai, Pei-Chi Lo, Akira Maeda, Han-Tang Wang, Rei Matsuura, Tasuku Kodama, Takehisa Ueno, Chihiro Takakura, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
Organizer
CAST 2017 in Cebu
Related Report
Int'l Joint Research
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[Presentation] Human DAF suppresses macrophage-mediated xenogeneic cytotoxicity and phagocytosis through the binding of SCR-4 to the inhibitory receptor2016
Author(s)
Rieko Sakai, Akira Maeda, Thuy-Vy Choi, Pei-Chi Lo, Rei Matsuura, Tasuku Kodama, Kazuaki Yamanaka, Kengo Nakahata, Tomomi Kawai, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
Organizer
International Complement Workshop
Place of Presentation
金沢市
Year and Date
2016-09-04
Related Report
Int'l Joint Research
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[Presentation] SCR-4 is required for CD55-induced suppression on macrophage-mediated cytotoxicity2016
Author(s)
Akira Maeda, Thuy-vy Choi, Pei-Chi Lo, Rieko Sakai, Mayumi Asada, Kazuaki Yamanaka, Kengo Nakahata, Rei Matsuura, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
Organizer
The Transplantation Society
Place of Presentation
香港(中国)
Year and Date
2016-08-20
Related Report
Int'l Joint Research
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[Presentation] Human CD200 suppresses the M0 macrophage-mediated cytotoxicity in xenotransplantation2016
Author(s)
Akira Maeda, Pei-Chi Lo, Thuy-vy Choi, Rieko Sakai, Mayumi Asada, Kazuaki Yamanaka, Kengo Nakahata, Rei Matsuura, Hiroshi Eguchi, Hiroomi Okuyama, Shuji Miyagawa
Organizer
The Transplantation Society
Place of Presentation
香港(中国)
Year and Date
2016-08-20
Related Report
Int'l Joint Research
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