Development of multidisciplinary therapy based on mechanism of liver insufficiency in a use of Aged partial graft after liver transplantation.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390324
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The University of Tokushima
• Principal Investigator: SHIMADA Mitsuo 徳島大学, ヘルスバイオサイエンス研究部, 教授 (10216070)
• Co-Investigator(Kenkyū-buntansha): YASUTOMO Koji 徳島大学, ヘルスバイオサイエンス研究部, 教授 (30333511) ; TANAKA Shinji 東京医科歯科大学, 情報処理センター, 科学技術振興特別特認准教授 (30253420) ; IMURA Satoru 徳島大学, 病院, 助教 (90380021) ; MORINE Yuji 徳島大学, 病院, 助教 (60398021) ; TAKEDA Eiji 徳島大学, ヘルスバイオサイエンス研究部, 教授 (00144973) ; UTSUNOMIYA Toru 徳島大学, ヘルスバイオサイエンス研究部, 准教授 (30304801) ; IKEMOTO Tetsuya 徳島大学, ヘルスバイオサイエンス研究部, 助教 (20398019) ; KATAGIRI Toyomasa 徳島大学, 疾患プロテオゲノム研究センター, 教授 (60291895) ; OYADOMARI Seiichi 徳島大学, 疾患プロテオゲノム研究センター, 教授 (90502534)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 肝不全 / 加齢肝 / 幹細胞 / 加齢遺伝子

Research Abstract

The majority of liver transplantation in Japan is living donor liver transplantation. As aging population has recently been increasing, aged liver of a donor candidate has become a most problem. We gave similar surgical insults as liver transplantation, including ischemia-reperfusion injury and massive hepatectomy in the aged liver. We obtained several novel findings regarding the mechanisms, by which aging induced liver functional and regenerative insufficiency. We also found some possible therapeutic agents and strategies including ADRC, HDAC inhibitor and the others, which may improve the liver dysfunction and may support liver regeneration in these animal models.

Research Products

• [Journal Article] Specific molecular signatures of non-tumor liver tissue may predict a risk of hepatocarcinogenesis (2014)
  • Author(s): Utsunomiya T, Shimada M, Morine Y, Tajima A, Imoto I
  • Journal Title: Cancer Sci
  • Peer Reviewed
• [Journal Article] The gene profile in the spleen under massive partial hepatectomy using cDNA microarray and pathway analysis (2014)
  • Author(s): Arakawa Y, Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Mori H, Kanamoto M, Iwahashi S, Saito Y, Takasu C
  • Journal Title: J Gastroenterol Hepatol
  • DOI: 10.1111/jgh.12573
  • Peer Reviewed
• [Journal Article] Abrogation of Rbpj attenuates experimental autoimmune uveoretinitis by inhibiting IL-22-producing CD4+ T cells (2014)
  • Author(s): Bhuyan ZA, Asanoma M, Iwata A, Ishifune C, Maekawa Y, Shimada M, Yasutomo K
  • Journal Title: PLoS One Volume: 9(2) Pages: e89266
  • DOI: 10.1371/journal.pone.0089266
  • Peer Reviewed
• [Journal Article] Cytokine expression in spleen affects progression of liver cirrhosis through liver-spleen cross-talk (2014)
  • Author(s): Asanoma M, Ikemoto T, Mori H, Utsunomiya T, Imura S, Morine Y, Iwahashi S, Saito Y, Yamada S, Shimada M
  • Journal Title: Hepatol Res
  • DOI: 10.1111/hepr.12267
  • Peer Reviewed
• [Journal Article] A hydrolyzed whey peptide-based diet ameliorates hepatic ischemia-reperfusion injury in the rat nonalcoholic fatty liver (2014)
  • Author(s): Nii A, Utsunomiya T, Shimada M, Ikegami T, Ishibashi H, Imura S, Morine Y, Ikemoto T, Sasaki H, Kawashima A
  • Journal Title: Surg Today
  • Peer Reviewed
• [Journal Article] Improving allogeneic islet transplantation by suppressing Th17 and enhancing Treg with histone deacetylase inhibitors (2014)
  • Author(s): Sugimoto K, Itoh T, Takita M, Shimoda M, Chujo D, SoRelle JA, Naziruddin B, Levy MF, Shimada M, Matsumoto S
  • Journal Title: Transpl Int Volume: 27(4) Pages: 408-415
  • DOI: 10.1111/tri.12265
  • Peer Reviewed
• [Journal Article] Recovery pattern of non-protein respiratory quotient and non-esterified fatty acids after liver resection (2014)
  • Author(s): Sugihara K, Yamanaka-Okumura H, Teramoto A, Urano E, Katayama T, Mori H, Utsunomiya T, Shimada M, Takeda E
  • Journal Title: Nutrition Volume: 30(4) Pages: 443-438
  • DOI: 10.1016/j.nut.2013.09.012
  • Peer Reviewed
• [Journal Article] Senescence-related genes possibly responsible for poor liver regeneration after hepatectomy in elderly patients (2014)
  • Author(s): Zhu C, Ikemoto T, Utsunomiya T, Yamada S, Morine Y, Imura S, Arakawa Y, Takasu C, Ishikawa D, Shimada M
  • Journal Title: J Gastroenterol Hepatol Volume: 29(5) Pages: 1102-1108
  • DOI: 10.1111/jgh.12468
  • Peer Reviewed
• [Journal Article] Trophic effect of adipose tissue-derived stem cells on porcine islet cells (2014)
  • Author(s): Yamada S, Shimada M, Utsunomiya T, Ikemoto T, Saito Y, Morine Y, Imura S, Mori H, Arakawa Y, Kanamoto M, Iwahashi S
  • Journal Title: J Surg Res Volume: 187(2) Pages: 667-672
  • DOI: 10.1016/j.jss.2013.10.031
  • Peer Reviewed
• [Journal Article] Preand postoperative nutritional assessment and health-related quality of life in recipients of living donor liver transplantation (2014)
  • Author(s): Urano E, Yamanaka-Okumura H, Teramoto A, Sugihara K, Morine Y, Imura S, Utsunomiya T, Shimada M, Takeda E
  • Journal Title: Hepatol Res
  • Peer Reviewed
• [Journal Article] Asanoma M. Beneficial effects of enteral nutrition containing with hydrolyzed whey peptide on warm ischemia/reperfusion injury in the rat liver (2014)
  • Author(s): Hanaoka J, Shimada M, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Mori H, Sugimoto K, Saito Y, Yamada S
  • Journal Title: Hepatol Res Volume: 44(1) Pages: 114-121
  • DOI: 10.1111/hepr.12097
  • Peer Reviewed
• [Journal Article] Beneficial effects of green tea catechin on massive hepatectomy model in rats (2014)
  • Author(s): Saito Y, Mori H, Takasu C, Komatsu M, Hanaoka J, Yamada S, Asanoma M, Ikemoto T, Imura S, Morine Y, Utsunomiya T, Shimada M
  • Journal Title: J Gastroenterol Volume: 49(4) Pages: 692-701
  • DOI: 10.1007/s00535-013-0799-9
  • Peer Reviewed
• [Journal Article] Effects of a whey peptide-based enteral formula diet on liver dysfunction following living donor liver transplantation (2014)
  • Author(s): Arakawa Y, Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Hanaoka J
  • Journal Title: Surg Today Volume: 44(1) Pages: 44-49
  • DOI: 10.1007/s00595-012-0466-4
  • Peer Reviewed
• [Journal Article] Effects of splenectomy on hepatic gene expression profiles after massive hepatectomy in rats (2013)
  • Author(s): Arakawa Y, Shimada M, Utsunomya T, Imura S, Morine Y, Ikemoto T, Takasu C
  • Journal Title: J Gastroenterol Hepatol Volume: 28(10) Pages: 1669-1677
  • DOI: 10.1111/jgh.12316
  • Peer Reviewed
• [Journal Article] Significance of sonic hedgehog signaling after massive hepatectomy in a rat (2013)
  • Author(s): Hanaoka J, Shimada M, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Mori H
  • Journal Title: Surg Today Volume: 43(3) Pages: 300-307
  • DOI: 10.1007/s00595-012-0248-z
  • Peer Reviewed
• [Journal Article] The protective effect of adipose-derived stem cells against liver injury by trophic molecules (2013)
  • Author(s): Saito Y, Shimada M, Utsunomiya T, Ikemoto T, Yamada S, Morine Y, Imura S, Mori H, Sugimoto K, Iwahashi S, Asanoma M
  • Journal Title: J Surg Res Volume: 180(1) Pages: 162-168
  • DOI: 10.1016/j.jss.2012.10.009
  • Peer Reviewed
• [Journal Article] Impact of a new refrigerator on the preservation of hepatic grafts (2012)
  • Author(s): Kanamoto M, Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Mori H, Hanaoka J
  • Journal Title: Hepatol Res Volume: 42(8) Pages: 798-805
  • Peer Reviewed
• [Journal Article] Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma (2012)
  • Author(s): Yamada S, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Mori H, Hanaoka J, Iwahashi S, Saito Y
  • Journal Title: Hepatol Res Volume: 42(5) Pages: 454-458
  • DOI: 10.1111/j.1872-034X.2011.00952.x
  • Peer Reviewed
• [Journal Article] Notch2 regulates the development of marginal zone B cells through Fos (2012)
  • Author(s): Iwahashi S, Maekawa Y, Nishida J, Ishifune C, Kitamura A, Arimochi H, Kataoka K, Chiba S, Shimada M, Yasutomo K
  • Journal Title: Biochem Biophys Res Commun Volume: 418(4) Pages: 701-707
  • DOI: 10.1016/j.bbrc.2012.01.082
  • Peer Reviewed
• [Journal Article] Possible utility of MRI using Gd-EOB-DTPA for estimating liver functional reserve (2012)
  • Author(s): Utsunomiya T, Shimada M, Hanaoka J, Kanamoto M, Ikemoto T, Morine Y, Imura S, Harada M
  • Journal Title: J Gastroenterol Volume: 47(4) Pages: 470-476
  • DOI: 10.1007/s00535-011-0513-8
  • Peer Reviewed
• [Journal Article] Impact of a new refrigerator for the preservation of whole blood (2012)
  • Author(s): Kanamoto M, Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Mori H, Hanaoka J
  • Journal Title: J Surg Res Volume: 173(1) Pages: 180-184
  • DOI: 10.1016/j.jss.2010.09.011
  • Peer Reviewed
• [Journal Article] Role of UCP2 expression after hepatic warm ischemia-reperfusion in the rat (2011)
  • Author(s): Ninomiya M, Shirabe K, Shimada M, Terashi T, Maehara Y
  • Journal Title: Gut Liver Volume: 5(4) Pages: 486-492
  • DOI: 10.5009/gnl.2011.5.4.486
  • Peer Reviewed
• [Journal Article] Human adipose-derived stem cells : potential clinical applications in surgery (2011)
  • Author(s): Utsunomiya T, Shimada M, Imura S, Morine Y, Ikemoto T, Mori H, Hanaoka J, Iwahashi S, Saito Y, Iwaguro H
  • Journal Title: Surg Today Volume: 41(1) Pages: 18-23
  • DOI: 10.1007/s00595-010-4415-9
  • Peer Reviewed
• [Journal Article] Beneficial effects of follistatin in hepatic ischemia-reperfusion injuries in rats (2011)
  • Author(s): Kanamoto M, Shimada M, Morine Y, Yoshizumi T, Imura S, Ikegami T, Mori H, Arakawa Y
  • Journal Title: Dig Dis Sci Volume: 56(4) Pages: 1075-1081
  • DOI: 10.1007/s10620-010-1401-4
  • Peer Reviewed
• [Presentation] Recent Advancements in Liver Surgery : Assessment of Funcional Reserve, Simulation and Navigation (2013)
  • Author(s): Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Arakawa Y , Kanamoto M, Iwahashi S, Saito Y , T akasu C, Y amada S
  • Organizer: International Association of Surgeons, Gastroenterologists and Oncologists 2013 (IASGO2013)
  • Place of Presentation: ルーマニア(The Palace of the Parliament)
  • Year and Date: 20130918-21
• [Presentation] The gene profile in the spleen under rat small-for-size graft model using cDNA microarray and pathway analaysis (2013)
  • Author(s): Arakawa Y , Shimada M, Ishikawa D, Y amada S, Saito Y , T akasu C, Iwahashi S, Kanamoto M, Mori H, Ikemoto T , Morine Y , Imura S, Utsunomiya T , Sato H, Miyake H
  • Organizer: The 13th Congress of the Asian Society Of Transplantation 2013 (CAST2013)
  • Place of Presentation: 京都府(国立京都国際会館)
  • Year and Date: 20130902-06
• [Presentation] The homing effect of adipose-derived stem cells to the injured liver : The shift of stromal cellderived factor 1 expressions (2013)
  • Author(s): Saito Y , Shimada M, Utsunomiya T , Ikemoto T , Y amada S, T akasu C.
  • Organizer: The 13th Congress of the Asian Society Of Transplantation 2013 (CAST2013)
  • Place of Presentation: 京都府(国立京都国際会館)
  • Year and Date: 20130902-06
• [Presentation] Successful management of liver transplant recipient with strongly positive donor-specific antibody against human leukocyte antigen (2013)
  • Author(s): Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Arakawa Y, Kanamoto M, Iwahashi S
  • Organizer: International Surgical Week 2013 (SW2013)
  • Place of Presentation: フィンランド(Helsinki Exhibition and Convention Centre)
  • Year and Date: 20130825-29
• [Presentation] Enkhbold Chinbold. One-Stop Shopping for 3-Dimensional Anatomy of Hepatic V asculature and Bile Duct with a Special Reference to Biliary Image Reconstruction (2012)
  • Author(s): Shimada M, Utsunomiya T , Imura S, Morine Y, Ikemoto T, Hanaoka J, Miyatani T , Saito Y , Yamada S
  • Organizer: American College Of Surgeons Annual Clinical Congress (ACS2012)
  • Place of Presentation: アメリカ(McCormick Place)
  • Year and Date: 20120930-04
• [Presentation] Impact of human adipose tissue derived regenerative cell for cryopreserved porcine islets (2012)
  • Author(s): Ikemoto T, Shimada M, Utsunomiya T, Imura S, Morine Y, Hanaoka J, Miyatani T , Kanamoto M
  • Organizer: 10 th World Congress of the International Hepato-Pancreato-Biliary Association (IHPBA2012)
  • Place of Presentation: フランス (Paris des Congres)
  • Year and Date: 20120701-05
• [Presentation] Bevacizumab ameliorates sinusoidal injury after oxaliplatin-based chemotherapy and enhances liver regeneration after hepatectomy (2011)
  • Author(s): Hanaoka J, Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Mori H, Saito Y , Y amada S, Asanoma M
  • Organizer: World Congress of the International Association of surgeons, Gastroenterologists and Oncologists(IASGO2011)
  • Place of Presentation: 京都(京王プラザホテル)
  • Year and Date: 20111109-12
• [Presentation] Cytoprotective effect of human adipose tissue derived stem cell on porcine islet cells (2011)
  • Author(s): Yamada S, Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Mori H, Hanaoka J, Kanamoto M, Iwahashi S, Saito Y , Asanoma M
  • Organizer: 12th Congress of the Asian Society of Transplantation (CAST2011)
  • Place of Presentation: 韓国 (COEX)
  • Year and Date: 20110925-28
• [Presentation] The possibility of adipose-derived stem cells for an alternative therapy for liver failure (2011)
  • Author(s): Saito Y , Shimada M, Utsunomiya T, Ikemoto T, Yamada S, Morine Y, Imura S, Mori H, Hanaoka J, Sugimoto K, Asanoma M
  • Organizer: 12th Congress of the Asian Society of Transplantation (CAST2011)
  • Place of Presentation: 韓国 (COEX)
  • Year and Date: 20110925-28
• [Presentation] Ischemia reperfusion injury enhances SDF1 expressions and homing of adipose derived regenerative cells in the liver (2011)
  • Author(s): Saito Y , Shimada M, Utsunomiya T , Morine Y, Imura S, Ikemoto T, Mori H, Hanaoka J, Sugimoto K, Y amada S, Asanoma M
  • Organizer: 8th International Smposium on Minimal Residual Cancer (ISMRC2011)
  • Place of Presentation: 大阪府(Grand Cube Osaka)
  • Year and Date: 20110921-23
• [Presentation] Regeneration of caudate lobe in extended left lobe graft including caudate lobe after living donor liver transplantation (2011)
  • Author(s): Shimada M, Imura S, Mori H, Morine Y, Ikemoto T, Hanaoka J, Kanamoto M, Iwahashi S, Saito Y , Asanoma M, Y amada S, Utsunomiya T
  • Organizer: European Society for Organ Transplantation (ESOT2011)
  • Place of Presentation: イギリス (SECC)
  • Year and Date: 20110904-07
• [Presentation] The possibility of adipose-derived regenerative cells for an alternative therapy for liver failure (2011)
  • Author(s): Mori H, Shimada M, Saito Y , Utsunomiya T , Imura S, Morine Y , Ikemoto T , Hanaoka J, Iwahashi S, Asanoma M, Y amada S
  • Organizer: European Society for Organ Transplantation (ESOT2011)
  • Place of Presentation: イギリス (SECC)
  • Year and Date: 20110904-07
• [Presentation] Whey protein isolate, MEIN[〇!R], can reduce liver damege early after living donor liver transplantation (2011)
  • Author(s): Ishikawa D, Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Mori H, Hanaoka J, Kanamoto M, Iwahashi S, Saito Y , Asanoma M, Kume H, Sasaki H
  • Organizer: European Society for Organ Transplantation (ESOT2011)
  • Place of Presentation: イギリス (SECC)
  • Year and Date: 20110904-07
• [Presentation] Green T ea Catechins Improve Liver Dysfunction Following Massive Hepatectomy Through Anti-Oxidative and Anti-Inflammatory Activities in Rat (2011)
  • Author(s): Saito Y , Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Mori H, Hanaoka J, Kanamoto M
  • Organizer: Digestive Disease Week (DDW2011)
  • Place of Presentation: アメリカ (McCormick Place)
  • Year and Date: 20110507-10