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A new selection system of suitable immunosuppressive drugs for each pancreatic islet transplantation using epigenetic analysis in a three-dimensional culture system

Research Project

Project/Area Number 24659596
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionMeiji University

Principal Investigator

MASAKI NAGAYA  明治大学, 公私立大学の部局等, 教授 (90329300)

Co-Investigator(Kenkyū-buntansha) NAGASHIMA Hiroshi  明治大学, 農学部, 教授 (50318664)
UMEYAMA Kazuhiro  明治大学, 研究・知財戦略機構, 特任准教授 (70342699)
WATANABE Masato  明治大学, 研究・知財戦略機構, 特任講師 (00321688)
ARAI Yoshikazu  明治大学, 研究・知財戦略機構, 研究推進員 (90614769)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords糖尿病 / 膵ランゲルハンス島 / 膵島移植 / 免疫抑制剤 / ヒト糖尿病類似モデルブタ / エピゲノム / パーソナライズド
Research Abstract

The problem with pancreatic islet transplantation for type 1 diabetes is that the immunosuppressive drugs used can damage pancreatic beta cells. This project aimed to establish a new selection system of suitable immunosuppressive drugs for each islet transplantation using epigenetic analysis in a three-dimensional culture system. We first isolated islets from a transgenic pig specifically expressing the green fluorescent protein in the beta cells. These islets were cultured in the presence of an immunosuppressive drug. Thereafter, epigenetic analysis of the islets was performed. With time, we observed epigenetic changes in the insulin gene promoter of the islets in a certain group, although there was no change in their configuration. Our system can evaluate the short-term influence of immunosuppressive drugs on pancreatic islets, the system may be used to determine which immunosuppressive drugs are specifically suitable for each human islet transplantation.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (39 results)

All 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (28 results) (of which Invited: 1 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Transgenic pigs with pancreas specific expression of green fluorescent protein2014

    • Author(s)
      Matsunari H, Kobayashi T, Watanabe M, Umeyama K, Nakano K, Kanai T, Mat suda T, Nagaya M, Hara M, Nakauchi H, Nagashima H
    • Journal Title

      J Reprod Dev

      Volume: (Epub ahead of print)

    • NAID

      130003390840

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transgenic pigs with pancreas specific expression of green fluorescent protein2014

    • Author(s)
      Matsunari H, Kobayashi T., Watanabe M, Umeyama K, Nakano K, Kanai T, Matsuda T, Nagaya M, Hara M, Nakauchi H, Nagashima H
    • Journal Title

      J Reprod Dev.

      Volume: Epub ahead of print

    • NAID

      130003390840

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Production of iabetic offspring using cryopreserved epididymal sperm by in vitro fertilization and intrafallopian insemination techniques in transgenic pigs2013

    • Author(s)
      Umeyama K, Honda K, Matsunari H, Nakano K, Hidaka T, Sekiguchi K, Mochizuki H, Takeuchi Y, Fu j iwara T, Watanabe M, Nagaya M, Nagashima H
    • Journal Title

      J Reprod Dev

      Volume: 59 Pages: 599-603

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs2013

    • Author(s)
      Matsunari H, Nagashima H, Watanabe M, Umeyama K, Nakano K, Nagaya M, Kobayashi T, Yamaguchi T, Sumazaki R, Herzenberg LA, Nakauchi H
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 110 Pages: 4557-62

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Production of diabetic offspring using cryopreserved epididymal sperm by in vitro fertilization and intrafallopian insemination techniques in transgenic pigs.2013

    • Author(s)
      Umeyama K, Honda K, Matsunari H, Nakano K, Hidaka T, Sekiguchi K, Mochizuki H, Takeuchi Y, Fujiwara T, Watanabe M, Nagaya M, Nagashima H.
    • Journal Title

      J Reprod Dev.

      Volume: 59 Pages: 599-603

    • NAID

      130003361059

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs.2013

    • Author(s)
      Matsunari H, Nagashima H, Watanabe M, Umeyama K, Nakano K, Nagaya M, Kobayashi T, Yamaguchi T, Sumazaki R, Herzenberg LA, Nakauchi H.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 110 Issue: 12 Pages: 4557-62

    • DOI

      10.1073/pnas.1222902110

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Advancing pig cloning technologies towards application in regenerativemedicine2012

    • Author(s)
      Nagashima H, Matsunari H, Nakano K, Watanabe M, Umeyama K, Nagaya M
    • Journal Title

      Reprod Domest Anim

      Volume: 47 Suppl 4 Pages: 120-6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Advancing pig cloning technologies towards application in regenerative medicine.2012

    • Author(s)
      Nagashima H, Matsunari H, Nakano K, Watanabe M, Umeyama K, Nagaya M.
    • Journal Title

      Domest Anim.

      Volume: Suppl 4 Issue: s4 Pages: 120-6

    • DOI

      10.1111/j.1439-0531.2012.02065.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] In vivo exogenic organ generation with organogenesis-disabled cloned pigs as a platform2014

    • Author(s)
      Matsunari H, Nakano K, Kanai T, Matsuda T, Maehara M, Watanabe M, Umeyama K, Nagaya M, Nakauchi H, Nagashima H
    • Organizer
      40th Annual Conference of the International Embryo Transfer Society
    • Place of Presentation
      Reno, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵臓欠損ブタ胎仔を用いた外来性細胞由来膵臓形成の試み2014

    • Author(s)
      松成ひとみ、浅野吉則、小林美里奈、内倉鮎子、渡邊將人、梅山一大、長屋昌樹、中内啓光、長嶋比呂志
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] In vivo exogenic organ generation with organogenesis-disabled cloned pigs as a platform.2014

    • Author(s)
      Matsunari H, Nakano K, Kanai T, Matsuda T, Maehara M, Watanabe M, Umeyama K, Nagaya M, Nakauchi H, Nagashima H
    • Organizer
      40th Annual Conference of the International Embryo Transfer Society
    • Place of Presentation
      Reno, USA.
    • Related Report
      2013 Annual Research Report
  • [Presentation] 膵臓欠損ブタ胎仔を用いた外来性細胞由来膵臓形成の試み.2014

    • Author(s)
      松成ひとみ、浅野吉則、小林美里奈、内倉鮎子、渡邊將人、梅山一大、長屋昌樹、中内啓光、長嶋比呂志.
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都.
    • Related Report
      2013 Annual Research Report
  • [Presentation] In vivo generation of exogenic pancreas in apancreatic cloned pigs via blastocyst complementation2013

    • Author(s)
      Matsunari H, Nakano K, Kanai T, Matsuda T, Maehara M, Watanabe M, Umeyama K, Nagaya M, Nakauchi H, Nagashima H
    • Organizer
      12th Congress of International Xenotransplantation Association
    • Place of Presentation
      Osaka
    • Related Report
      2013 Final Research Report
  • [Presentation] Generation of a double-transgenic pig with pancreas-specific green and liver-specific red fluorescence2013

    • Author(s)
      Matsunari H, Nakano K, Kanai T, Sakai R, Watanabe M, Umeyama K, Kobayashi T, Yamaguchi T, Shiota A, Nagaya M, Nakauchi H, Nagashima H
    • Organizer
      39th Annual Conference of the International Embryo Transfer Society
    • Place of Presentation
      Hannover, Germany
    • Related Report
      2013 Final Research Report
  • [Presentation] Production of chimeric porcine fetuses by aggregation method using parthenogenetic embryos2013

    • Author(s)
      Nakano K, Watanabe M, Matsunari H, Matsuda T, Honda K, Maehara M, Kanai T, Hayashida G, Kobayashi M, Umeyama K, Fujishiro S, Mizukami Y Nagaya M, Hanazono Y, Nagashima H
    • Organizer
      39th Annual Conference of the International Embryo Transfer Society
    • Place of Presentation
      Hannover, Germany
    • Related Report
      2013 Final Research Report
  • [Presentation] ガラス化保存された体外成熟/体外受精胚を用いた糖尿病モデル遺伝子改変ブタの作出2013

    • Author(s)
      松村幸奈,前原美樹,本田香澄,林田豪太,倉本桃子,中野和明,松成ひとみ,小林美里奈,内倉鮎子,浅野吉則,渡邊将人,梅山一大,長屋昌樹,長嶋比呂志
    • Organizer
      第106回日本繁殖生物学会大会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] In vivo generation of exogenic pancreas in apancreatic cloned pigs via blastocyst complementation.2013

    • Author(s)
      Matsunari H, Nakano K, Kanai T, Matsuda T, Maehara M, Watanabe M, Umeyama K, Nagaya M, Nakauchi H, Nagashima H.
    • Organizer
      12th Congress of International Xenotransplantation Association (IXA)
    • Place of Presentation
      Osaka, Japan.
    • Related Report
      2013 Annual Research Report
  • [Presentation] ガラス化保存された体外成熟/体外受精胚を用いた糖尿病モデル遺伝子改変ブタの作出.2013

    • Author(s)
      松村幸奈, 前原美樹, 本田香澄, 林田豪太, 倉本桃子, 中野和明, 松成ひとみ, 小林美里奈, 内倉鮎子, 浅野吉則, 渡邊将人, 梅山一大, 長屋昌樹, 長嶋比呂志
    • Organizer
      第106回日本繁殖生物学会大会:
    • Place of Presentation
      東京.
    • Related Report
      2013 Annual Research Report
  • [Presentation] Generation of a double-transgenic pig with pancreas-specific green and liver-specific red fluorescence.2013

    • Author(s)
      Matsunari H, Nakano K, Kanai T, Sakai R, Watanabe M, Umeyama K, Kobayashi T, Yamaguchi T, Shiota A, Nagaya M, Nakauchi H, Nagashima H.
    • Organizer
      39th Annual Conference of the International Embryo Transfer Society
    • Place of Presentation
      Hannover, Germany
    • Related Report
      2012 Research-status Report
  • [Presentation] Production of chimeric porcine fetuses by aggregation method using parthenogenetic embryos.2013

    • Author(s)
      Nakano K, Watanabe M, Matsunari H, Matsuda T, Honda K, Maehara M, Kanai T, Hayashida G, Kobayashi M, Umeyama K, Fujishiro S, Mizukami Y, Nagaya M, Hanazono Y, Nagashima H.
    • Organizer
      39th Annual Conference of the International Embryo Transfer Society
    • Place of Presentation
      Hannover, Germany
    • Related Report
      2012 Research-status Report
  • [Presentation] 遺伝子改変ブタ・クローンブタのトランスレーショナルリサーチへの応用2012

    • Author(s)
      長嶋比呂志、松成ひとみ、渡邊将人、梅山一大、長屋昌樹
    • Organizer
      日本実験動物医学会
    • Place of Presentation
      大分県
    • Year and Date
      2012-05-23
    • Related Report
      2013 Final Research Report
  • [Presentation] In vitro modeling of al-antitrypsin deficiency using induced pluripotent stem cell-derived hepatocytes froma 1-antitrypsin deficient patients2012

    • Author(s)
      Tafaleng EN, Han B, Hale P, Nagaya M, Duncan SA, Sto l s DB, Strom SC, Fox IJ
    • Organizer
      The 63rd annual meeting of the American Association for the Study of Liver disease
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Transmission and expression of a retrovirally introduced red fluorescent protein gene in successive generations of transgenic pigs2012

    • Author(s)
      Kanai T, Matsunari H, Takeuchi Y, Honda K, Maehara M, Nakano K, Takayanagi S, Watanabe M, Umeyama K, Tada N, Onodera M, Nagaya M, Nakauchi H, Nagashima H
    • Organizer
      International Congress on Animal Reproduction
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Development of a feasible verification system for pluripotent stem cells using porcine parthenogenetic embryos2012

    • Author(s)
      Nakano K, Watanabe M, Matsunari H, Matsuda T, Honda K, Maehara M, Kanai T, Arai Y, Umeyama K, Fu j i shiro S, Nagaya M, Nagashima H
    • Organizer
      10^<th> International Societ for Stem Cell Research
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Final Research Report
  • [Presentation] 遠赤色蛍光蛋白monomeric Plumを発現するトランスジェニックブタの作出とその利用2012

    • Author(s)
      渡邊將人、松成ひとみ、小林美里奈、中野和明、竹内靖浩、前原美樹、金井貴博、松村幸奈、林田豪太、倉本桃子、坂井理恵子、梅山一大、渡辺信之、小野寺雅史、長屋昌樹、長嶋比呂志
    • Organizer
      第35回日本分子生物学会大会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] ブタ単為発生胚を用いた凝集キメラ作出法2012

    • Author(s)
      中野和明、渡邊將人、松成ひとみ、松田泰輔、本田香澄、前原美樹、竹内靖浩、金井貴博、新井良和、梅山一大、藤城修平、長屋昌樹、花園豊、長嶋比呂志
    • Organizer
      第105回日本繁殖生物学会大会
    • Place of Presentation
      筑波
    • Related Report
      2013 Final Research Report
  • [Presentation] 膵・肝二色蛍光発現するトランスジェニックブタの開発2012

    • Author(s)
      松成ひとみ、金井貴博、坂井理恵子、中野和明、渡邊將人、梅山一大、高柳就子、小林俊寛、山口智之、塩田明、長屋昌樹、中内啓光、長嶋比呂志
    • Organizer
      第105回日本繁殖生物学会大会
    • Place of Presentation
      筑波
    • Related Report
      2013 Final Research Report
  • [Presentation] 遠赤色蛍光蛋白monomeric Plumを発現するトランスジェニックブタの作出2012

    • Author(s)
      渡邊將人、松成ひとみ、小林美里奈、中野和明、前原美樹、金井貴博、松村幸奈、林田豪太、倉本桃子、坂井理恵子、梅山一大、渡邊信之、小野寺雅史、長屋昌樹、長嶋比呂志
    • Organizer
      第105回日本繁殖生物学会大会
    • Place of Presentation
      筑波
    • Related Report
      2013 Final Research Report
  • [Presentation] 再生医療研究のための大型動物モデルの開発2012

    • Author(s)
      長嶋比呂志、松成ひとみ、中野和明、渡邊将人、梅山一大、長屋昌樹
    • Organizer
      第12回日本抗加齢医学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 遠赤色蛍光蛋白monomeric Plumを発現するトランスジェニックブタの作出とその応用2012

    • Author(s)
      渡邊將人、松成ひとみ、小林美里奈、中野和明、竹内靖浩、前原美樹、金井貴博、松 村幸奈、林田豪太、倉本桃子、坂井理恵子、梅山一大、渡辺信之、小野寺雅史、長屋 昌樹、長嶋比呂志
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 遠赤色蛍光蛋白monomeric Plumを発現するトランスジェニックブタの作出2012

    • Author(s)
      渡邊將人、松成ひとみ、小林美里奈、中野和明、前原美樹、金井貴博、松村幸奈、林 田豪太、倉本桃子、坂井理恵子、梅山一大、渡辺信之、小野寺雅史、長屋昌樹、長嶋 比呂志
    • Organizer
      第105回日本繁殖生物学会大会
    • Place of Presentation
      つくば市、筑波大学
    • Related Report
      2012 Research-status Report
  • [Presentation] 膵・肝二色蛍光発現するトランスジェニックブタの開発2012

    • Author(s)
      松成ひとみ、金井貴博、坂井理恵子、中野和明、渡邊將人、梅山一大、高柳就子、小 林俊寛、山口智之、塩田明、長屋昌樹、中内啓光、長嶋比呂志
    • Organizer
      第105回日本繁殖生物学会大会
    • Place of Presentation
      つくば市、筑波大学
    • Related Report
      2012 Research-status Report
  • [Presentation] ブタ単為発生胚を用いた凝集キメラ作出法2012

    • Author(s)
      中野和明、渡邊將人、松成ひとみ、松田泰輔、本田香澄、前原美樹、竹内靖浩、金井 貴博、新井良和、梅山一大、藤城修平、水上善久、長屋昌樹、花園豊、長嶋比呂志
    • Organizer
      第105回日本繁殖生物学会大会
    • Place of Presentation
      つくば市、筑波大学
    • Related Report
      2012 Research-status Report
  • [Presentation] In vitro modeling of alpha-1-antitrypsin deficiency using induced pluripotent stem cell-derived hepatocytes from alpha-1-antitrypsin deficient patients.2012

    • Author(s)
      Tafaleng EN, Han B, Hale P, Soto-Gutierrez A, Nagaya M, Duncan SA, Stols DB, Strom SC, Fox IJ
    • Organizer
      The 63rd annual meeting of the American Association for the Study of Liver disease,
    • Place of Presentation
      Boston, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Development of a feasible verification system for pluripotent stem cells using porcine parthenogenetic embryos2012

    • Author(s)
      Nakano K, Watanabe M, Matsunari H, Matsuda T, Honda K, Maehara M, Kanai T, Arai Y, Umeyama K, Fujishiro S, Nagaya M, Nagaya M, Nagashima H
    • Organizer
      10th International Society for Stem Cell Research
    • Place of Presentation
      Yokohama
    • Related Report
      2012 Research-status Report
  • [Presentation] 遺伝子改変ブタ・クローンブタのトランスレーショナルリサーチへの応用

    • Author(s)
      長嶋比呂志、松成ひとみ、中野和明、渡邊将人、梅山一大、長屋昌樹
    • Organizer
      日本実験動物医学会
    • Place of Presentation
      大分
    • Related Report
      2012 Research-status Report
    • Invited
  • [Remarks] 明治大学バイオリソース研究国際インスティチュート

    • URL

      http://muiibr.com/institute/institute.html

    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 免疫抑制剤の評価方法、及び免疫抑制剤評価キット2014

    • Inventor(s)
      長屋昌樹,長嶋比呂志
    • Industrial Property Rights Holder
      長屋昌樹,長嶋比呂志
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-027655
    • Filing Date
      2014-02-17
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 免疫抑制剤の評価方法、及び免疫抑制剤評価キット.2014

    • Inventor(s)
      長屋昌樹, 長嶋比呂志
    • Industrial Property Rights Holder
      長屋昌樹, 長嶋比呂志
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2014-027655
    • Filing Date
      2014-02-17
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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