Research of hepatocyte transplantation for injured liver and surgical stress .

• Project/Area Number: 23791489
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Sapporo Medical University
• Principal Investigator: NAKAMURA YUKIO 札幌医科大学, 医学部, 研究員 (50516648)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 肝臓外科学 / 肝細胞移植 / 脂肪性肝炎 / アポトーシス / 再生医療

Research Abstract

In recently, surgical management of hepatocellular carcinoma should be addressed for non-viral hepatitis and liver cirrhosis. We attempt to apply liver replacement therapy using hepatocyte transplantation for clinical therapy. In order to achieve it, we developed rat liver replacement model which imitated clinical human NASH/NAFLD. In this model, we revealed a cell physiology of the transplanted cells which generated bile duct linage cells. In addition, we succeded to increase survival rate in NASH liver cirrhotic model. In the clinical research, we reported a benefit and default of donor cell procurement. We also revealed that a clinical value of BTR, ATIII, and GSA. We classified various liver functional indicators using clustering analysis.

Research Products

• [Journal Article] New technique of extracorponeal hepatic inflow control for pure laparoscopic liver resection (2013)
  • Author(s): Mizuguchi T, Kawamoto M, Nakamura Y, Meguro M, Harada K, OtaS, Hui TT, and Hirata K.
  • Journal Title: Surg Laparosc Endosc Percutan Tech Volume: (in press)
  • Peer Reviewed
• [Journal Article] Differentiation capacity of hepatic stem/progenitor cells isolated from D-galactosamine-treated rat livers. (2013)
  • Author(s): Norihisa Ichinohe, Tanimizu N, Ooe H, Nakamura Y, Mizuguchi T, Hirata K, Kon J, Mitaka T
  • Journal Title: Hepatology Volume: 57 Issue: 3 Pages: 1192-1202
  • DOI: 10.1002/hep.26084
  • Peer Reviewed
• [Journal Article] Hepatic biliary epithelial cells acquire epithelial integrity but lose plasticity to differentiate into hepatocytes in vitro during development. (2013)
  • Author(s): Tanimizu N, Nakamura Y, Ichinohe N, Mizuguchi T, Hirata K, Mitaka T.
  • Journal Title: J Cell Sci Volume: 126 Pages: 5239-5246
  • DOI: 10.1242/jcs.133082
  • Peer Reviewed
• [Journal Article] Prognosis and Predictors of Surgical Complications in Hepatocellular Carcinoma Patients With or Without Cirrhosis after Hepatectomy. (2013)
  • Author(s): Mizuguchi T, Kawamoto M, Meguro M, Nakamura Y, Ota S, Hui TT, Hirata K.
  • Journal Title: World J Surg. Volume: 37 Issue: 6 Pages: 1379-1387
  • DOI: 10.1007/s00268-013-1989-6
  • Peer Reviewed
• [Journal Article] Continuous monitoring of central venous oxygen saturation predicts postoperative liver dysfunction after liver resection. (2013)
  • Author(s): Meguro M, Mizuguchi T, Kawamoto M, Nakamura Y, Ota S, Kukita K, Ishii M, Tatsumi H, Hirata K.
  • Journal Title: Surgery Volume: 154 Issue: 2 Pages: 351-362
  • DOI: 10.1016/j.surg.2013.04.039
  • Peer Reviewed
• [Journal Article] Preoperative hepatocyte transplantation improves the survival of rats with non -alcoholic steatohepatitis-related cirrhosis after partial hepatectomy (2013)
  • Author(s): Nakamura Y, Mizuguchi T, Tanimizu N, Ichinohe N, Ooe H, Kawamoto M, Meguro M, Hirata K, Mitaka T.
  • Journal Title: Cell Transplant Volume: e pub Pages: 1243-1254
  • DOI: 10.3727/096368913x668649
  • Peer Reviewed / Open Access
• [Journal Article] Serum antithrombin III level is well correlated with multiple indicators for assessment of liver function and diagnostic accuracy for predicting postoperative liver failure in hepatocellular carcinoma patients (2012)
  • Author(s): Mizuguchi T, Kawamoto M, Meguro M, Son S, Nakamura Y, Harada K, Shibata T, Ota S, Hirata K.
  • Journal Title: Hepatogastroenterology Volume: 59 Pages: 551-7
  • Peer Reviewed
• [Journal Article] Low-dose steroid pretreatment ameliorates the transient impairment of liver regeneration (2012)
  • Author(s): Shibata T, et al
  • Journal Title: World Journal of Gastroenterology Volume: 18 Issue: 9 Pages: 905-914
  • DOI: 10.3748/wjg.v18.i9.905
  • Peer Reviewed
• [Journal Article] Laparoscopic hepatectomy : a systematic review, meta-analysis and power analysis (2011)
  • Author(s): Mizuguchi T, Kawamoto M, Meguro M, Shibata T, Nakamura Y, Kimura Y, Furuhata T, Sonoda T, Hirata K.
  • Journal Title: Surg Today Volume: 41 Issue: 1 Pages: 39-47
  • DOI: 10.1007/s00595-010-4337-6
  • NAID: 10027818558
  • Peer Reviewed
• [Journal Article] Prognostic impact of preoperative the branched-chain amino acid to the tyrosine ratio in hepatocellular carcinoma patients after initial hepatectomy (2011)
  • Author(s): Mizuguchi T, et al
  • Journal Title: Journal of Gastrointestinal Surgery Volume: 15 Issue: 8 Pages: 1433-1439
  • DOI: 10.1007/s11605-011-1566-y
  • Peer Reviewed
• [Journal Article] Cluster analysis of indicators of liver functional and preoperative low branched-chain amino acid tyrosine ration indicate a high risk of early recurrence in analysis of 165 hepatocellular carcinoma patients after initial hepatectomy (2011)
  • Author(s): Nakamura Y, et al
  • Journal Title: Surgery Volume: 150 Issue: 2 Pages: 250-262
  • DOI: 10.1016/j.surg.2011.06.001
  • Peer Reviewed
• [Presentation] Continuous monitoring of central venous oxygen saturation predicts postoperative liver dysfunction after liver resection (2013)
  • Author(s): Meguro M, Mizuguch T, Kawamoto M, Nakamura Y, Kukita K, Ota S, Hirata K.
  • Organizer: 8th Annual Academic Surgical Congress, Oral presentation
  • Place of Presentation: New Orleans, LO, USA
• [Presentation] 肝細胞癌における細胞外マトリックスの分子環境―ラミニンa鎖と受容体ルテランによる分子機序 (2013)
  • Author(s): 水口 徹、吉川大和、谷水直樹、一戸義久、中村幸雄、川本雅樹、目黒誠、野水基義、三高俊広、平田公一
  • Organizer: 第113日本外科学会定期学術集会
  • Place of Presentation: 博多市
• [Presentation] Thy1-positive cell transplantation activates the growth of small hepatocyte-like progenitor cells in rat livers treated with retrorsine and PH. (2013)
  • Author(s): Mitaka T, Ichinohe N, Kon J, Tanimizu N, Nakamura Y, Mizuguchi T, Hirata K.
  • Organizer: Experimental Biology 2013
  • Place of Presentation: Boston, USA
• [Presentation] 食餌により誘導した肝障害ラットに対する肝細胞移植の有用性についての検討 (2013)
  • Author(s): 中村 幸雄、水口 徹、川本 雅樹、目黒 誠、 信岡 隆幸、木村 康利、古畑 智久、平田 公一、谷水 直樹、三高 俊広、村田 雅樹、澤田 典均
  • Organizer: 第67回日本消化器外科学会
  • Place of Presentation: 富山
• [Presentation] Hepatic Progenitor Cell Transplantation for Improving Survival after Liver Resection of Rat Non-alcoholic Steatocirrhotic Liver Model (2012)
  • Author(s): Nakamura Y, Mizuguchi T, Ohe H, Kawamoto K, Meguro M, Ota S, Mitaka T, Hirata K.
  • Organizer: 7th Annual Academic Surgical Congress, Quick shot oral presentation
  • Place of Presentation: Las Vegas, NV, USA
• [Presentation] Extracorporeal hepatic inflow control method for pure laparoscopic liver resection (2012)
  • Author(s): Mizuguchi T, Kawamoto K, Meguro M, Nakamura Y, Harada K, Nobuoka T, Kimura Y, Furuhata T, Hirata K.
  • Organizer: 7th Annual Academic Surgical Congress, Quick shot oral presentation
  • Place of Presentation: Las Vegas, NV, USA
• [Presentation] Hepatic Progenitor Cell Transplantation for Improving Survival after Liver Resection in a Rat Non-Alcoholic Steatocirrhotic Liver Model (2012)
  • Author(s): Y. Nakamura, T. Mizuguchi, M. Kawamoto, M. Meguro, S. Ota, T. Mitaka, K. Hirata
  • Organizer: 7th Annual Academic Surgical Congress
  • Place of Presentation: Las Vegus
• [Presentation] ラット肝硬変モデルにおける肝細胞移植の影響についての検討 (2011)
  • Author(s): 中村幸雄、水口徹、三高俊広、平田公一
  • Organizer: 第66回消化器外科学会総会
  • Place of Presentation: 名古屋
• [Book] SURGERY FRONTIER (2011)
  • Author(s): 中村幸雄、水口徹、三高俊広、平田公一
  • Total Pages: 453
  • Publisher: 障害肝と肝細胞移植