Preclinical study on protection strategy and function recovery strategy of preimplantation for marginal graft

• Project/Area Number: 26293355
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Fujita Health University
• Principal Investigator: Kusaka Mamoru 藤田保健衛生大学, 医学部, 教授 (40309141)
• Co-Investigator(Kenkyū-buntansha): 山田 和彦 鹿児島大学, 学内共同利用施設等, 教授 (40241103) ; 佐原 寿史 鹿児島大学, 学内共同利用施設等, 准教授 (90452333)
• Co-Investigator(Renkei-kenkyūsha): HOSHINAGA Kiyotaka 藤田保健衛生大学, 医学部, 教授 (30229174)
• Research Collaborator: MIURA Kouhei ; KAWAI Akihiro ; WAKI Shiori
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
• Keywords: 移植・再生医療 / 腎移植 / 常温腎臓持続体外灌流保存 / マージナルドナー / 臓器保護 / 前臨床実験 / ミニブタ / 虚血再潅流障害 / 移植 再生医療 / 一酸化炭素 / HMGB1 / 虚血再灌流障害

Outline of Final Research Achievements

In this study, we focused on agents with various cytoprotective effects on marginal donor kidneys where activation of inflammatory precursors caused tissue injury. Using established MHC miniture swine which can evaluate detailed immune reaction, we investigated the effect of organ protection and repair by drug administration to donor, recipient, graft persistent perfusion preservation. We conducted experiments to establish a strategy to restore and recover marginal donor organs to conditions comparable to living organs.

Research Products

• [Journal Article] 特集「毒ガス？いいえ治療薬です」．【新たな治療薬としての一酸化炭素への期待】 (2016)
  • Author(s): 佐原寿史, 関島光裕, 山田和彦
  • Journal Title: 臨床麻酔 Volume: 39(6) Pages: 855-864
• [Journal Article] Combined predictive value of the expanded donor criteria for long-term graft survival of kidneys from donors after cardiac death: A single-center experience over three decades. (2016)
  • Author(s): Kusaka M, Kubota Y, Sasaki H, Fukami N, Fujita T, Hirose Y, Takahashi H, Kenmochi T, Shiroki R, Hoshinaga K.
  • Journal Title: Int J Urol. Volume: 23(4) Issue: 4 Pages: 319-324
  • DOI: 10.1111/iju.13045
  • Peer Reviewed / Open Access
• [Journal Article] Kidney Transplantation, Cardiovascular Risk, and Long-Term Dialysis in Japan. (2016)
  • Author(s): Tada M, Hasegawa M, Sasaki H, Kusaka M, Shiroki R, Hoshinaga K, Ito T, Kenmochi T, Nakai S, Takahashi K, Hayashi H, Koide S, Yuzawa Y.
  • Journal Title: Transplant Proc. Volume: 48(1) Issue: 1 Pages: 26-30
  • DOI: 10.1016/j.transproceed.2015.12.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Post-Transplant Membranous Nephropathy Associated with Chronic Active Antibody-Mediated Rejection and Hepatitis C Infection after Deceased Donor Renal Transplantation (2016)
  • Author(s): Doke T, Sato W, Takahashi K, Hayashi H, Koide S, Sasaki H, Kusaka M, Shiroki R, Hoshinaga K, Takeda A, Yuzawa Y, Hasegawa M.
  • Journal Title: Internal Medicine Volume: 55 Issue: 4 Pages: 375-380
  • DOI: 10.2169/internalmedicine.55.5468
  • NAID: 130005125800
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Robot-assisted partial nephrectomy: Superiority over laparoscopic partial nephrectomy. (2015)
  • Author(s): Shiroki R, Fukami N, Fukaya K, Kusaka M, Natsume T, Ichihara T, Toyama H.
  • Journal Title: Int J Urol. Volume: 23(2) Issue: 2 Pages: 122-131
  • DOI: 10.1111/iju.13001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 特集「毒ガス？いいえ治療薬です」．【新たな治療薬としての一酸化炭素への期待】． (2015)
  • Author(s): 佐原寿史, 関島光裕, 山田和彦
  • Journal Title: 臨床麻酔 Volume: 39(6) Pages: 855-864
• [Journal Article] Initial Experience With a Tailor-made Simulation and Navigation Program Using a 3-D Printer Model of Kidney Transplantation Surgery. (2015)
  • Author(s): Kusaka M, Sugimoto M, Fukami N, Sasaki H, Takenaka M, Anraku T, Ito T, Kenmochi T, Shiroki R, Hoshinaga K.
  • Journal Title: Transplant Proc. Volume: 47（3） Issue: 3 Pages: 596-599
  • DOI: 10.1016/j.transproceed.2014.12.045
  • NAID: 40020688799
  • Peer Reviewed / Open Access
• [Journal Article] Nutritional Status in Japanese Renal Transplant Recipients With Long-term Graft Survival. (2015)
  • Author(s): Sasaki H, Suzuki A, Kusaka M, Fukami N, Shiroki R, Itoh M, Takahashi H, Uenishi K, Hoshinaga K.
  • Journal Title: Transplant Proc. Volume: 47（2） Issue: 2 Pages: 367-372
  • DOI: 10.1016/j.transproceed.2014.10.013
  • Peer Reviewed / Open Access
• [Journal Article] Serum liver-type fatty acid-binding protein predicts recovery of graft function after kidney transplantation from donors after cardiac death (2014)
  • Author(s): Kawai A, Kusaka M, Kitagawa F, Ishii J, Fukami N, Maruyama T, Sasaki H, Shiroki R, Kurahashi H, Hoshinaga K
  • Journal Title: Clin Transplant Volume: 28 Issue: 6 Pages: 749-754
  • DOI: 10.1111/ctr.12375
  • Peer Reviewed / Open Access
• [Journal Article] Protective effect of neutralization of the extracellular high-mobility group box-1 on renal ischemia-reperfusion injury in miniature swine. (2014)
  • Author(s): Miura K, Sahara H, Sekijima M, Kawai A, Waki S, Nishimura H, Setoyama K, Clayman ES, Shimizu A, Yamada K.
  • Journal Title: Transplantation Volume: Nov 15;98(9) Issue: 9 Pages: 937-943
  • DOI: 10.1097/tp.0000000000000358
  • Peer Reviewed
• [Presentation] 温虚血腎に対する移植前常温持続灌流の有用性－MHC確立クラウン系ミニブタを用いた慢性腎移植 (2016)
  • Author(s): 有吉勇一, 佐原寿史, 関島光裕, 室川剛廣, 岩永健裕, 市成ゆりか, 山田和彦
  • Organizer: 第4回日本先進医工学ブタ研究会
  • Place of Presentation: 静岡県 三島市
  • Year and Date: 2016-10-17
• [Presentation] Adopting the Kidney Donor Profile Index (KDPI)/ Kidney Donor Risk Index (KDRI) for Japanese Donors after Cardiac Death (2016)
  • Author(s): Kusaka M, Kawai A, Fukami N, Sasaki H, Takahashi H, Ito T, Kenmochi T, Shiroki R, Hoshinaga K.
  • Organizer: 2016 American Transplant Congress (ATC)
  • Place of Presentation: Boston USA
  • Year and Date: 2016-06-11
  • Int'l Joint Research
• [Presentation] The Combined Predictive Value of the ECD Criteria for Long-term Graft Survival of Kidneys from Donors after Cardiac Death: A Single-center Experience over Three Decades (2015)
  • Author(s): Kusaka M, Kubota Y, Sasaki H, Takenaka M, Fukami N, Takahashi H, Ito T, Kenmochi T, Shiroki R, Hoshinaga K.
  • Organizer: 13th Congress of the International Society for Organ Donation and Procurement (ISOPD)
  • Place of Presentation: Seoul Korea
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] シンポジウム2「実験用ブタ施設の現状と今後の動向」高度前臨床移植実験：医用ミニブタを用いた大動物実験として果たすべき役割と課題． (2015)
  • Author(s): 山田和彦
  • Organizer: 第3回日本先進医工学ブタ研究会
  • Place of Presentation: 東京 日本大学会館
  • Year and Date: 2015-10-16
• [Presentation] シンポジウム5「実験用ブタを用いた各種応用研究」Medical Gasを用いた新たな移植医療：硫化水素の有用性． (2015)
  • Author(s): 佐原寿史、関島光裕、岩永健裕、市成ゆりか、山田和彦
  • Organizer: 第3回日本先進医工学ブタ研究会
  • Place of Presentation: 東京 日本大学会館
  • Year and Date: 2015-10-16
• [Presentation] MHC-inbred CLAWN miniature swine as preclinical large animal model for transplantation. (2015)
  • Author(s): Sahara H, Iwanaga T, Sekijima M, Waki S, Ichinari Y, Shimizu A, Yamada K
  • Organizer: The 14th Congress of the Asian Society of Transplantation.
  • Place of Presentation: Singapore
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] Initial Experience with a Tailor-made Simulation and Navigation Program Using a 3D Printer Model of Kidney Transplantation Surgery (2015)
  • Author(s): Kusaka M, Sugimoto M, Fukami N, Sasaki H, Ito T, Kenmochi T, Shiroki R, Hoshinaga K.
  • Organizer: 2015 American Transplant Congress (ATC)
  • Place of Presentation: Philadelphia USA
  • Year and Date: 2015-05-02
  • Int'l Joint Research
• [Presentation] 「医用ミニブタを用いた前臨床研究」．クラウンミニブタを用いた移植モデルとMedical Gas (2015)
  • Author(s): 佐原寿史、山田和彦
  • Organizer: 第3回公開シンポジウム先進医用ミニブタの開発と前臨床研究拠点形成プロジェクト
  • Place of Presentation: 鹿児島市
  • Year and Date: 2015-03-25
• [Presentation] 「臨床医としての医用ミニブタを用いた研究」.腎移植医療の問題点とその対策 (2015)
  • Author(s): 日下 守、佐原寿史、関島光裕、山田和彦
  • Organizer: 第3回公開シンポジウム先進医用ミニブタの開発と前臨床研究拠点形成プロジェクト
  • Place of Presentation: 鹿児島市
  • Year and Date: 2015-03-25
  • Invited
• [Presentation] Combined Predictive Value of ECD Criteria for Long-term Graft Survival of Kidneys from Donors after Cardiac Death (2014)
  • Author(s): Kusaka M, Kubota Y, Takahashi H, Fukami N, Sasaki H, Kenmochi T, Shiroki R, Hoshinaga K.
  • Organizer: World Transplant Congress 2014
  • Place of Presentation: San Francisco
  • Year and Date: 2014-07-26 – 2014-07-31
• [Presentation] Long-term Graft Survival Was Affected by Several Donor’s Factors in Renal Transplants Engrafting DCD Kidneys. – Based on Data from A Single Center Having Recovered over 500 DCD Renal Grafts – (2014)
  • Author(s): Hoshinaga K, Kusaka M, Takahashi H, Kubota Y, Fukami N, Sasaki H, Kenmochi T, Shiroki R,
  • Organizer: World Transplant Congress 2014
  • Place of Presentation: San Francisco
  • Year and Date: 2014-07-26 – 2014-07-31
• [Presentation] Serum High-mobility Group Box-1 (HMGB-1) Kinetics after Kidney Transplantation from Donors after Cardiac Death (2014)
  • Author(s): Kusaka M, Takenaka M, Fukami N, Sasaki H, Ito T, Kenmochi T, Shiroki R, Hoshinaga K.
  • Organizer: World Transplant Congress 2014
  • Place of Presentation: San Francisco
  • Year and Date: 2014-07-26 – 2014-07-31
• [Presentation] MHC確立クラウンミニブタによる新規治療・医療機器開発を目指す前臨床試験 (2014)
  • Author(s): 佐原寿史
  • Organizer: BIO tech 2014 アカデミーフォーラム
  • Place of Presentation: 東京
  • Year and Date: 2014-05-14 – 2014-05-16
• [Remarks] 鹿児島大学医用ミニブタ・先端医療開発研究センター
  • URL: http://www.kufm.kagoshima-u.ac.jp/~xenotx/
• [Remarks] 鹿児島大学医用ミニブタ・先端医療開発センター
  • URL: http://www.kufm.kagoshima-u.ac.jp/~xenotx/