Influence of prevention of ischemic reperfusion and liver regeneration by rejuvunated liver through gene insertion

• Project/Area Number: 26861087
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Nagasaki University
• Principal Investigator: HIDAKA Masaaki 長崎大学, 病院(医学系), 助教 (10457541)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 老化 / 肝再生 / 生体肝移植 / 高齢ドナー / 肝グラフト / 移植 / 虚血再灌流

Outline of Final Research Achievements

We investigated that anti-aging gene affected the outcome about the model of ischemic reperfusion on elderly mice because the outcome from elderly donor in living donor liver transplantation (LDLT) was worse than the younger donor. We investigated the expression of macrophage in the donor liver in LDLT and influence of liver macrophage to the outcome after LDLT. There were a few macrophages in elderly donor than in younger donor on the liver biopsy. The infectious complications after LDLT was independently happened in less macrophage group in elderly donor. Multivariate analysis showed that the less macrophage was independent factor of graft loss of LDLT in elderly donor. We investigated the comparison of the expression of anti-aging gene between younger and elderly mice. Also we investigated the expression of anti-aging gene, inflammation cytokine in the ischemic reperfusion model in the rodent. The anti-aging gene was not more expressed in the elderly mice by anti-aging agent.

Research Products

• [Journal Article] Aspartate transaminase-platelet ratio and Fibrosis-4 indices as effective markers for monitoring esophageal varices in HIV/hepatitis C virus co-infected patients due to contaminated blood products for hemophilia. (2017)
  • Author(s): Natsuda K, Takatsuki M, Tanaka T, Soyama A, Adachi T, Ono S, Hara T, Baimakhanov Z, Imamura H, Okada S, Hidaka M, Eguchi S.
  • Journal Title: Hepatology Research Volume: 印刷中 Issue: 12 Pages: 1282-1288
  • DOI: 10.1111/hepr.12866
  • Peer Reviewed
• [Journal Article] In vivo construction of liver tissue by implantation of a hepatic non-parenchymal/adipose-derived stem cell sheet (2017)
  • Author(s): Mio Fujii, Kosho Yamanouchi, Yusuke Sakai, Zhassulan Baimakhanov, Izumi Yamaguchi, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Tamotsu Kuroki, Susumu Eguchi
  • Journal Title: Journal of Tissue Engineering and Regenerative Medicine Volume: 印刷中 Issue: 1 Pages: e287-e295
  • DOI: 10.1002/term.2424
  • Peer Reviewed
• [Journal Article] he kupffer cell number affects the outcome of living donor liver transplantation from elderly donors. (2016)
  • Author(s): Hidaka M, Eguchi S, Takatsuki M, Soyama A, Ono S, Adachi T, Natsuda K, Kugiyama T, Hara T, Okada S, Imamura H, Miuma S, Miyaaki H.
  • Journal Title: Transplantation Direct Volume: 2 Issue: 8 Pages: e94-e94
  • DOI: 10.1097/txd.0000000000000608
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Analysis of early relaparotpmy following living donor liver transplantation. (2016)
  • Author(s): Hara T, Soyama A, Hidaka M, Kitasato A, Ono S, Natsuda K, Kugiyama T, Imamura H, Okada S, Baimakhanov Z, Kuroki T, Eguchi S.
  • Journal Title: Liver transplantation Volume: 22 Issue: 11 Pages: 1519-1525
  • DOI: 10.1002/lt.24500
  • Peer Reviewed
• [Journal Article] Equal distribution of MSCs after hepatic ischemia reperfusion injury (2016)
  • Author(s): Askhat Isbambetov, Zhassulan Baimakhanov, Akihiko Soyama, Masaaki Hidaka, Yusuke Sakai, Mitsuhisa Takatsuki, Tamotsu Kuroki, Susumu Eguchi
  • Journal Title: Journal of Surgical Research Volume: 203 Issue: 2 Pages: 360-367
  • DOI: 10.1016/j.jss.2016.03.057
  • Peer Reviewed
• [Journal Article] Up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver (2016)
  • Author(s): Shuai Zhang, Tao-Sheng Li, Akihiko Soyama, Takayuki Tanaka, Chen Yan, Yusuke Sakai, Masaaki Hidaka, Ayaka Kinoshita, Koji Natsuda, Mio Fujii, Tota Kugiyama, Zhassulan Baimakhanov, Tamotsu Kuroki, Weili Gu, Susumu Eguchi
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 26540-26540
  • DOI: 10.1038/srep26540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The First Case of Deceased Donor Liver Transplantation for a Patient with End-Stage Liver Cirrhosis Due to Human Immunodeficiency Virus and Hepatitis C Virus Coinfection in Japan (2016)
  • Author(s): Eguchi S, Takatsuki M, Soyama A, Hidaka M, Kugiyama T, Natsuda K, Adachi T, Kitasato A, Fujita F, Kuroki T.
  • Journal Title: Japanese Journal of Infectious Diseases Volume: 69 Issue: 1 Pages: 80-82
  • DOI: 10.7883/yoken.JJID.2015.121
  • NAID: 130005120241
  • ISSN: 1344-6304, 1884-2836
  • Peer Reviewed
• [Journal Article] Does the development of chronic kidney disease and acute kidney injury affect the prognosis after living donor liver transplantation? (2016)
  • Author(s): Inoue Y, Soyama A, Takatsuki M, Hidaka M, Kinoshita A, Natsuda K, Baimakhanov Z, Kugiyama T, Adachi T, Kitasato A, Kuroki T, Eguchi S.
  • Journal Title: Clin Transplant. Volume: 30 Issue: 5 Pages: 518-27
  • DOI: 10.1111/ctr.12715
• [Journal Article] Hybrid procedure in living donor liver transplantation. (2015)
  • Author(s): Soyama A, Takatsuki M, Hidaka M, Adachi T, Kitasato A, Kinoshita A, Natsuda K, Baimakhanov Z, Kuroki T, Eguchi S.
  • Journal Title: Transplant Proc. Volume: 47 Pages: 679-82
  • NAID: 120006986912
  • Peer Reviewed
• [Journal Article] E-cadherin expression in hepatocellular carcinoma treated with previous local treatment in patients undergoing living donor liver transplantation. (2015)
  • Author(s): Kugiyama T, Hidaka M, Soyama A, Takatsuki M, Natsuda K, Kinoshita A, Carpenter I, Adachi T, Kitasato A, Kuroki T, Eguchi S.
  • Journal Title: Transplant Proc. Volume: 47 Issue: 3 Pages: 700-2
  • DOI: 10.1016/j.transproceed.2015.02.017
  • Peer Reviewed
• [Journal Article] A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis E in Liver Transplant Recipients in Japan. (2015)
  • Author(s): Inagaki Y, Oshiro Y, Tanaka T, Yoshizumi T, Okajima H, Ishiyama K, Nakanishi C, Hidaka M, Wada H, Hibi T, Takagi K, Honda M, Kuramitsu K, Tanaka H, Tohyama T, Ikegami T, Imura S, Shimamura T, Nakayama Y, Urahashi T, Yamagishi K, Ohnishi H, Nagashima S, Takahashi M, Shirabe K, Kokudo N, Okamoto H, Ohkohchi N.
  • Journal Title: EBioMedicine. Volume: 24 Pages: 1607-1612
  • NAID: 120005980821
  • Peer Reviewed
• [Journal Article] Acute and chronic postsurgical pain after living liver donation: Incidence and predictors. (2015)
  • Author(s): Soyama A, Takatsuki M, Hidaka M, Imamura H, Kuroki T, Eguchi S.
  • Journal Title: Liver Transpl. Volume: 21 Issue: 8 Pages: 1109-1109
  • DOI: 10.1002/lt.24125
  • Peer Reviewed
• [Journal Article] Technical refinement of hepatic vein reconstruction in living donor liver transplantation using left liver graft. (2015)
  • Author(s): Takatsuki M, Soyama A, Hidaka M, Kinoshita A, Baimakhanov Z, Kugiyama T, Adachi T, Kitasasto A, Kuroki T, Eguchi S.
  • Journal Title: Ann Transplant. Volume: 25 Pages: 290-6
  • DOI: 10.12659/aot.893136
  • NAID: 120006987029
  • Peer Reviewed
• [Journal Article] A Method for Performing Islet Transplantation Using Tissue-Engineered Sheets of Islets and Mesenchymal Stem Cells. (2015)
  • Author(s): Hirabaru M, Kuroki T, Adachi T, Kitasato A, Ono S, Tanaka T, Matsushima H, Sakai Y, Soyama A, Hidaka M, Yamanouchi K, Takatsuki M, Okano T, Eguchi S.
  • Journal Title: Tissue Eng Part C Methods. Volume: 21 Issue: 12 Pages: 1205-15
  • DOI: 10.1089/ten.tec.2015.0035
  • Peer Reviewed
• [Journal Article] Vascularized subcutaneous human liver tissue from engineered hepatocyte/fibroblast sheets in mice (2015)
  • Author(s): Yusuke Sakai, Kosho Yamanouchi, Kazuo Ohashi, Makiko Koike, Rie Utoh, Hideko Hasegawa, Izumi Muraoka, Takashi Suematsu, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Tamotsu Kuroki, Susumu Eguchi
  • Journal Title: Biomaterials Volume: 65 Pages: 66-75
  • DOI: 10.1016/j.biomaterials.2015.06.046
  • NAID: 120006986875
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Efficacy of multi-layered hepatocyte sheet transplantation for radiation-induced liver damage and partial hepatectomy in a rat model (2015)
  • Author(s): Zhassulan Baimakhanov, Kosho Yamanouchi, Yusuke Sakai, Makiko Koike, Akihiko Soyama, Masaaki Hidaka, Mitsuhisa Takatsuki, Fumihiko Fujita, Kengo Kanetaka, Tamotsu Kuroki, Susumu Eguchi
  • Journal Title: Cell Transplantation Volume: 25 Issue: 3 Pages: 549-558
  • DOI: 10.3727/096368915x688669
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sox9 expression in carcinogenesis and its clinical significance in intrahepatic cholangiocarcinoma. (2015)
  • Author(s): Matsushima H, Kuroki T, Kitasato A, Adachi T, Tanaka T, Hirabaru M, Hirayama T, Kuroshima N, Hidaka M, Soyama A, Takatsuki M, Kinoshita N, Sano K, Nishida N, Eguchi S.
  • Journal Title: Dig Liver Dis. Volume: 47 Issue: 12 Pages: 1067-75
  • DOI: 10.1016/j.dld.2015.08.003
  • Peer Reviewed / Open Access
• [Journal Article] Rapid production of engineered human primary hepatocyte/fibroblast sheets (2015)
  • Author(s): Yusuke Sakai, Makiko Koike, Akihiko Soyama, Masaaki Hidaka, Tamotsu Kuroki, Susumu Eguchi
  • Journal Title: Data in Brief Volume: 5 Pages: 498-501
  • DOI: 10.1016/j.dib.2015.09.044
  • NAID: 120006986862
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CD4 T lymphocyte counts in patients undergoing splenectomy during living donor liver transplantation. (2015)
  • Author(s): Natsuda K, Eguchi S, Takatsuki M, Soyama A, Hidaka M, Hara T, Kugiyama T, Baimakhanov Z, Ono S, Kitasato A, Fujita F, Kanetaka K, Kuroki T.
  • Journal Title: Transpl Immunol. Volume: 34 Pages: 50-3
  • DOI: 10.1016/j.trim.2015.11.004
  • Peer Reviewed
• [Journal Article] The efficacy of the ImmuKnow assay for evaluating the immune status in human immunodeficiency virus and hepatitis C virus-coinfected patients. (2014)
  • Author(s): Natsuda K, Soyama A, Takatsuki M, Hidaka M, Kitasato A, Adachi T, Kuroki T, Eguchi S.
  • Journal Title: Transplant Proc. Volume: 46 Pages: 733-735
  • Peer Reviewed
• [Journal Article] Analysis of the hepatic functional reserve, portal hypertension, and prognosis of patients with human immunodeficiency virus/hepatitis C virus coinfection through contaminated blood products in Japan. (2014)
  • Author(s): Eguchi S, Takatsuki M, Soyama A, Hidaka M, Nakao K, Shirasaka T, Yamamoto M, Tachikawa N, Gatanaga H, Kugiyama Y, Yatsuhashi H, Ichida T, Kokudo N.
  • Journal Title: Transplant Proc. Volume: 46 Pages: 736-738
  • NAID: 120006986593
  • Peer Reviewed
• [Journal Article] Obstructing spontaneous major shunt vessels might not be mandatory to maintain adequate portal inflow in living donor liver transplantation. (2014)
  • Author(s): Takatsuki M, Baimakhanov Z, Soyama A, Inoue Y, Hidaka M, Kuroki T, Eguchi S.
  • Journal Title: Transplantation. Volume: 97 Pages: 52-53
  • NAID: 120006986502
  • Peer Reviewed
• [Journal Article] How to explant a diseased liver for living donor liver transplantation after previous gastrectomy with severe adhesion (with video). (2014)
  • Author(s): Eguchi S, Soyama A, Takatsuki M, Hidaka M, Adachi T, Kitasato A, Baimakhanov Z, Kuroki T.
  • Journal Title: J Hepatobiliary Pancreat Sci. Volume: 21 Pages: 62-64
  • Peer Reviewed
• [Journal Article] The Impact of Treated Bacterial Infections within One Month before Living Donor Liver Transplantation in Adults. (2014)
  • Author(s): Hara T, Soyama A, Takatsuki M, Hidaka M, Carpenter I, Kinoshita A, Adachi T, Kitasato A, Kuroki T, Eguchi S.
  • Journal Title: Ann Transplant. Volume: 19 Pages: 674-679
  • NAID: 120006986290
  • Peer Reviewed
• [Presentation] Outcomes of LT, Hepatic resection, Local therapy for HCC less than 3 cm and 3 nodules (2016)
  • Author(s): Masaaki Hidaka, Akihiko Soyama, Tomohiko Adachi, Shinichiro Ono, Koji Natsuda, Takanobu Hara, Fumihiko Fujita, Kengo Kanetaka, Mitsuhisa Takatsuki, Susumu Eguchi
  • Organizer: World Congress of International college of surgeons
  • Place of Presentation: 京都市、京都府 京都国際会館
  • Year and Date: 2016-11-23
  • Int'l Joint Research
• [Presentation] 生体肝移植レシピエントにおいて免疫グロブリンG(IgG)値が術後感染症、短期成績に与える影響 (2016)
  • Author(s): 日高匡章 曽山明彦 足立智彦 大野慎一郎 夏田孔史 原 貴信 岡田怜美 今村一歩 濱田隆志 バイマカノフ・ジャスラン 高槻光寿 江口 晋
  • Organizer: 第34回 日本肝移植研究会
  • Place of Presentation: 旭川市、北海道 大雪ホール
  • Year and Date: 2016-07-28
• [Presentation] 腹部領域におけるAcute care surgery teamの取り組み －地方国立大学における取り組み－ (2016)
  • Author(s): 日高匡章 曽山明彦 北里 周 大野慎一郎 猪熊孝美 井上悠介 夏田孔史 永川寛徳 藤田文彦 金高賢悟 黒木 保 田崎 修 江口 晋
  • Organizer: 第52回日本腹部救急医学会
  • Place of Presentation: 京王プラザホテル（東京都・新宿区）
  • Year and Date: 2016-03-03
• [Presentation] 組織学的脈管侵襲を伴わない肝細胞癌の特徴と切除成績 (2015)
  • Author(s): 日高匡章 曽山明彦 高槻光寿 足立智彦 北里 周 田中貴之 木下綾華 夏田孔史 川上悠介 釘山統太 今村一歩 藤田文彦 金高賢悟 黒木 保 江口 晋
  • Organizer: JDDW 2015
  • Place of Presentation: グランドプリンス新高輪他（東京都・港区）
  • Year and Date: 2015-10-23
• [Presentation] 血液型不適合生体肝移植の長期成績と免疫学的検討 (2015)
  • Author(s): 日高匡章 曽山明彦 夏田孔史 大野慎一郎、北里 周、釘山統太、原 貴信、岡田怜美、今村一歩、Zhassulan Baimakhanov、藤田文彦、金高賢悟、黒木 保、江口 晋
  • Organizer: 第51回日本移植学会
  • Place of Presentation: ホテル日航熊本他（熊本県・熊本市）
  • Year and Date: 2015-10-02
• [Presentation] 3cm, 3個以下の肝細胞癌に対する肝切除、肝移植、内科的治療の治療成績 (2015)
  • Author(s): 日高匡章 曽山明彦 高槻光寿 足立智彦 北里 周 木下綾華 夏田孔史 釘山統太 藤田文彦 金高賢悟 田浦直太 宮明寿光 三馬 聡 黒木 保 中尾一彦 江口 晋
  • Organizer: 第105回日本消化器病学会九州支部例会
  • Place of Presentation: ホテルニュー長崎（長崎県・長崎市）
  • Year and Date: 2015-06-19
• [Presentation] 術前化学療法を施行した大腸癌肝転移症例に対するアシアロシンチを用いた肝切除基準の妥当性 (2015)
  • Author(s): 日高匡章 高槻光寿 曽山明彦 木下綾華 足立智彦 北里 周 カーペンターいづみ 田中貴之 ジャスラン・バイマカノフ 夏田孔史 釘山統太 藤田文彦 金高賢悟 黒木 保 江口 晋
  • Organizer: 第27回日本肝胆膵外科学会
  • Place of Presentation: ホテル グランパシフィック LE DAIBA（東京都・港区）
  • Year and Date: 2015-06-11
• [Presentation] 当科における高齢レシピエントの成績 -ドナー年齢、グラフト重量からの検討- (2015)
  • Author(s): 日高匡章 高槻光寿 曽山明彦 足立智彦 北里 周 田中貴之 木下綾華 夏田孔史 釘山統太 今村一歩 Zhassulan Baimakhanov 黒木 保 江口 晋
  • Organizer: 第33回 日本肝移植研究会
  • Place of Presentation: ホテルオークラ神戸（兵庫県・神戸市）
  • Year and Date: 2015-05-28
• [Presentation] 肝細胞癌に対する肝切除成績に術中門脈圧が及ぼす影響について (2015)
  • Author(s): 日高匡章 曽山明彦 高槻光寿 北里 周 夏田孔史 原 貴信 釘山統太 今村一歩 田中貴之 大野慎一郎 黒木 保 江口 晋
  • Organizer: 第3回九州門脈圧亢進症研究会
  • Place of Presentation: 第一三共株式会社九州支店7階会議室（福岡県・福岡市）
  • Year and Date: 2015-05-16
• [Presentation] 末期硬変肝における早期肝細胞癌診断の限界と免疫組織学的特徴‐移植摘出肝全肝検索からの検討‐ (2015)
  • Author(s): 日高匡章 高槻光寿 江口 晋
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: ホテル日航熊本他（熊本県・熊本市）
  • Year and Date: 2015-05-11
• [Presentation] アシアロシンチLHL15を用いた当科の肝切除基準の妥当性 (2015)
  • Author(s): 日高匡章 高槻光寿 曽山明彦 足立智彦 北里 周 カーペンターいづみ 田中貴之 木下綾華 夏田孔史 釘山統太 Zhassulan Bimakanov 藤田文彦 金高賢悟 黒木 保 江口 晋
  • Organizer: 第115回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-04-16
• [Presentation] 生体肝移植における高齢ドナーグラフトの治療成績－クッパー細胞からの検討－ (2014)
  • Author(s): 日高 匡章
  • Organizer: 第32回日本肝移植研究会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-07-02 – 2014-07-04