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2002 Fiscal Year Annual Research Report

骨髄細胞移植による肝組織再構築に関する研究

Research Project

Project/Area Number 13307037
Research InstitutionNihon University

Principal Investigator

高山 忠利  日本大学, 医学部, 教授 (30280944)

Co-Investigator(Kenkyū-buntansha) 成瀬 勝俊  東京大学, 医学部, 助手 (50291323)
三木 健司  東京大学, 医学部, 助手 (10242059)
幕内 雅敏  東京大学, 医学部, 教授 (60114641)
大石 均  日本大学, 医学部, 助手 (50277430)
加藤 高明  日本大学, 医学部, 講師 (40233788)
Keywords骨髄幹細胞 / 脱メチル化 / 分化誘導 / Cell fusion
Research Abstract

2001年度において、マウス肝非実質細胞と骨髄細胞の共培養によって、骨髄細胞より、アルブミンおよびサイトケラチン8陽性の肝細胞特異的遺伝子発現細胞への分化を誘導することに成功した。本年度は引き続き、骨髄細胞を肝細胞へ分化させる因子について検討した。5'azacytidine前処理、肝不全患者血清、オンコスタチンM、非実質細胞との接触の4つの因子が肝細胞への分化誘導に強く影響していることが明らかになった。近年、骨髄由来細胞が分化転換したと考えられた細胞が、細胞融合による見かけ上の変化であるという報告が認められたことより、これを実証するために、LacZトランスジェニックマウスの肝非実質細胞とGFP陽性骨髄細胞を共培養した。GFPおよびLacZを共発現する細胞は認められず、肝細胞に似た細胞コロニーは骨髄細胞より分化したものと判定した。RT-PCRにより共培養した骨髄由来の細胞は、アルブミン、CK8の他CK19も発現しており、胆管上皮細胞への分化も認められた。また、無処理の骨髄細胞にAFPが発現していることが明らかになったため、肝再生時の骨髄中のAFPの発現を調べた。特異的に肝細胞に取り込まれDNA合成を阻害する薬物である2-AAFを投与後に70%肝切除を行ったマウスと70%肝切除を行ったマウスの骨髄中のAFPmRNAの発現をPCRで測定した。2-AAF肝切除群ではAFPの発現は肝切除後2日目に約70倍に増加し、約2週間で前値に復した。肝切除群では肝切除3日目に約10倍まで増加し2週間で前値に復した。2-AAF投与により肝再生が抑制された状態では、骨髄中で肝細胞への分化が進んでおりこの肝前駆細胞が血流に乗って肝臓に運ばれるのではないかと考えている。組織障害時に骨髄中で障害組織の前駆細胞が誘導されたとする報告は認められず、骨髄細胞による組織障害の修復メカニズムを解明する上で極めて重要な知見が得られたと考えている。現在、骨髄細胞を、蛍光標識抗AHFP抗体で染色しFACSでAFP陽性細胞分画の同定を試みている。

  • Research Products

    (77 results)

All Other

All Publications (77 results)

  • [Publications] Takayama T: "Prevention of hepatocellular carcinoma recurrence : actuality and perspectives"Hepatogastroenterology. 49・43. 87-90 (2002)

  • [Publications] Makuuchi M: "Reasons for an exchange between eastern and western approach to patients with HCC"Hepatogastroenterology. 49・43. 74-81 (2002)

  • [Publications] Makuuchi M: "Progress in surgical treatment of hepatocellular carcinoma"Oncology. 62・1. 74-81 (2002)

  • [Publications] Kato K: "Pseudomonas aeruginosa infection and cystic fibrosis"Laracet. 359・9302. 262 (2002)

  • [Publications] Makuuchi M: "Remodeling the surgical approach to hepatocellular carcinoma"Hepatogastroenterology. 49・43. 36-40 (2002)

  • [Publications] Naruse K: "Development and perspectives of bioartificial liver support"Hepatogastroenterology. 49・43. 91-95 (2002)

  • [Publications] Sugawara Y: "Living-donor liver transplantation in an HIV-positive patient with hemophilia"Transplantation. 74・11. 1655-1656 (2002)

  • [Publications] Sugawara Y: "Spontaneous revascularization of arterial thrombosis after living donor liver transplantatio n"Abdom Imaging. 27・5. 546-548 (2002)

  • [Publications] Sugawara Y: "Successful treatment of hepatitis C virus after liver transplantation from an identical twin"Transplantation. 73・11. 1850-1851 (2002)

  • [Publications] Sugawara Y: "Preoperative portal embolization in patients with hepatocellular carcinoma"World J Surg. 26・1. 105-110 (2002)

  • [Publications] Surman OS: "Some ethical and psychiatric aspects of right-lobe liver transplantation in the United States and Japan"Psychosomatics. 43・5. 347-353 (2002)

  • [Publications] Torzilli G: "Ultrasound-guided liver resections for hepatocellular carcinoma"Hepatogastroenterology. 49・43. 21-27 (2002)

  • [Publications] Sugawara Y: "Living donor liver transplantation in a patient with HIV"Nippon Rinsho. 60・4. 803-806 (2002)

  • [Publications] Sugawara Y: "Duct-to-duct biliary reconstruction in living-related liver transplantation"Transplantation. 73・8. 1348-1350 (2002)

  • [Publications] Sugawara Y: "Safe donor hepatectomy for living related liver transplantation"Liver Transpl. 8・1. 58-62 (2002)

  • [Publications] Sugawara Y: "Right lateral sector graft in adult living-related liver transplantation"Transplantation. 73・1. 111-114 (2002)

  • [Publications] Sugawara Y: "Left liver plus caudate lobe graft with complete revascularization"Surgery. 132・5. 904-905 (2002)

  • [Publications] Sugawara Y: "Small-for-size graft problems in adult-to-adult living donor liver transplantation"Nippon Geka Gakkai Zasshi. 103・5. 419-42 (2002)

  • [Publications] Sugawara Y: "Anticoagulant therapy against hepatic artery thrombosis in living donor liver transplantation"Transplant Proc. 34・8. 3325-3326 (2002)

  • [Publications] Sugawara Y: "Living donor liver transplantation for fulminant hepatic failure"Transplant Proc. 34・8. 3287-3288 (2002)

  • [Publications] Sugawara Y: "Outflow reconstruction in recipients of right liver graft from living donors"Liver Transpl. 8・2. 167-168 (2002)

  • [Publications] Sugawara Y: "Living donor liver transplantation in adults: recent advances and results"Surgery. 132・2. 348-352 (2002)

  • [Publications] Sugawara Y: "Correlation between optimal tacrolimus doses and the graft weight in living donor liver transplantation"Clin Transplant. 16・2. 102-106 (2002)

  • [Publications] Sugawara Y: "New venoplasty technique for the left liver plus caudate lobe in living donor liver transplantation"Liver Transpl. 8・1. 76-77 (2002)

  • [Publications] Sajura A: "Gene expression profile during acute rejection in rat-to-mouse concordant cardiac xenograft by means of DNA microarray"Transpl Int. 15・11. 535-540 (2002)

  • [Publications] Sakamoto Y: "Advantage in using living donors with aberrant hepatic artery for partial liver graft arterialization"Transplantation. 74・4. 518-521 (2002)

  • [Publications] Sakamoto Y: "Anterior segmentectomy of the pancreatic head for islet cell tumors"Pancreas. 24・3. 317-319 (2002)

  • [Publications] Sano K: "Evaluation of hepatic venous congestion: proposed indication criteria for hepatic vein reconstruction"Ann Surg. 236・2. 241-247 (2002)

  • [Publications] Sata M: "Hematopojetic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis"Nat Med. 8・4. 403-409 (2002)

  • [Publications] Seyama Y: "Intermittent total vascular exclusion in removing caudate lobe tumor with tumor thrombus in the vena cava"Surgery. 131・5. 574-576 (2002)

  • [Publications] Midorikawa Y: "Development of well-differentiated hepatocellular carcinoma in large adenomatous hyperplasia after long-term follow-up : a case report"Hepatogastroenterology. 49・46. 1098-1101 (2002)

  • [Publications] Midorikawa Y: "Identification of genes associated with dedifferentiation of hepatocellular carcinoma with expression profiling analysis"Jpn J Cancer Res. 93・6. 636-643 (2002)

  • [Publications] Natori T: "G-CSF stimulates angiogenesis and promotes tumor growth : potential contribution of bone marrow-derived endothelial progenitor cells"Biochem Biophys Res Commun. 297・4. 1058-1061 (2002)

  • [Publications] Ohkubo T: "Successful pancreatic duct-to-jejunum anastomosis in a patient with a double pancreatic duct: usefulness of intraoperative ultrasonography (IQUS) and IQUS-guided pancreatography"Hepatogastroenterology. 49・48. 1724-1725 (2002)

  • [Publications] Ohkubo T: "Early induction of nerve growth factor-induced genes after liver resection-reperfusion injury"J Hepatol. 36・2. 210-217 (2002)

  • [Publications] Saiura A: "Detection of an up-regulation of a group of chemokine genes in murine cardiac allograft in the absence of interferon-gamma by means of DNA microarray"Transplantation. 73・9. 1480-1486 (2002)

  • [Publications] Kokudo N: "Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma: minimum surgical margins for successful resection"Arch Surg. 137・7. 833-840 (2002)

  • [Publications] Kubota K: "Small bile duct reconstruction of the caudate lobe in living-related liver transplantation"Ann Surg. 235・2. 174-177 (2002)

  • [Publications] Leelaudomlipi S: "Volumetric analysis of liver segments in 155 living donors"Liver Transpl. 8・7. 612-614 (2002)

  • [Publications] Li X: "Deregulation of G1/S transition is a common event in carcinoma of the ampulla of vater"Hepatogastroenterology. 49・47. 1239-1244 (2002)

  • [Publications] Maema A: "Spatially selective laser coagulation of the gastric wall : a new methodology"J Surg Res. 103・1. 114-120 (2002)

  • [Publications] Maema A: "Impaired volume regeneration of split livers with partial venous disruption : a latent problem in partial liver transplantation"Transplantation. 73・5. 765-769 (2002)

  • [Publications] Kanda T: "Fulminant hepatic failure associated with triazolam"Dig Dis Sci. 47・5. 1111-1114 (2002)

  • [Publications] Kaneko J: "Aspergillus osteomyelitis after liver transplantation"Liver Transpl. 8・11. 1073-1075 (2002)

  • [Publications] Kaneko J: "Normal splenic volume in adults by computed tomography"Hepatogastroenterology. 49・48. 1726-1727 (2002)

  • [Publications] Kobayashi T: "Effects of amrinone on hepatic ischemia-reperfusion injury in rats"J Hepatol. 37・1. 31-38 (2002)

  • [Publications] Kobayashi T: "Telomerase expression and p53 status in hepatocellular carcinoma"Am J Gastroenterol. 97・12. 3166-3171 (2002)

  • [Publications] Kokudo N: "Extent of resection and outcome after curative resection for intrahepatic cholangiocarcinoma"Surg Oncol Clin N Am. 11・4. 969-983 (2002)

  • [Publications] Hashikura Y: "Recent advance in living donor liver transplantation"World J Surg. 26・2. 243-246 (2002)

  • [Publications] Hirata M: "Immunosuppressive effect of chenodeoxycholic acid on natural killer cell activity in patients with biliary atresia and hepatitis C virus-related liver cirrhosis"Dig Dis Sci. 47・5. 1100-1106 (2002)

  • [Publications] Hirata M: "Gastrointestinal bleeding after living-related liver transplantation"Dig Dis Sci. 47・11. 2386-2388 (2002)

  • [Publications] Hui AM: "Proliferative marker Ki-67 in gallbladder carcinomas: high expression level predicts early recurrence after surgical resection"Cancer Lett. 176・2. 191-198 (2002)

  • [Publications] Ijichi M: "alpha-Fetoprotein mRNA in the circulation as a predictor of postsurgical recurrence of hepatocellular carcinoma: a prospective study"Hepatology. 35・4. 853-860 (2002)

  • [Publications] Imamura H: "Pringle's manoeuvre in living donors"Lancet. 360・9350. 2049-2050 (2002)

  • [Publications] Fukunishi I: "Psychiatric problems in living-re1ated transplantation (III) : pretransplant psychological assessment in living-related transplantation"Transplant Proc. 34・7. 2628-2629 (2002)

  • [Publications] Fukunishi I: "Association between pretransplant psychological assessments and posttransplant psychiatric disorders in living-related transplantation. Psychosomatics"Psychosomatics. 43・1. 49-54 (2002)

  • [Publications] Guo L: "Prolonged survival in rat liver transplantation with mouse monoclonal antibody against an inducible costimulator (ICOS)"Transplantation. 73・7. 1027-1032 (2002)

  • [Publications] Gyu Lee S: "Modified right liver graft from a living donor to prevent congestion"Transplantation. 74・1. 54-59 (2002)

  • [Publications] Hasegawa K: "Hepatocellular carcinoma originating from intramural cells in the bile duct"Hepatogastroenterology. 49・48. 1688-1691 (2002)

  • [Publications] Hasegawa K: "Effect of hypoventilation on bleeding during hepatic resection: a randomized controlled trial"Arch Surg. 137・3. 311-315 (2002)

  • [Publications] Cescon M: "Right liver graft without middle hepatic vein reconstruction from a living donor"Transplantation. 73・7. 1164-1166 (2002)

  • [Publications] Cescon M: "Role of splenectomy in living-donor liver transplantation for adults"Hepatogastroenterology. 49・45. 721-723 (2002)

  • [Publications] Egami S: "Effect of pediatric living-donor liver transplantation on splenomegaly"Transplantation. 74・11. 1639-1642 (2002)

  • [Publications] Fukunishi I: "Maladjustment behaviors in pediatric living-related transplantation"Transplant Proc. 34・7. 2767 (2002)

  • [Publications] Fukunishi I: "Psychiatric problems in living-related transplantation (II) : the association between paradoxical psychiatric syndrome and guilt feelings in adult recipients after living donor liver transplantation"Transplant Proc. 34・7. 2632-2633 (2002)

  • [Publications] Fukunishi I: "Psychiatric problems in living-related transplantation (I) : Incidence rate of psychiatric disorders in living-related transplantation"Transplant Proc. 34・7. 2630-2631 (2002)

  • [Publications] Torzilli G: "Living-donor liver transplantation in an HIV-positive patient with hemophilia"Transplantation. 74・11. 1655-1656 (2002)

  • [Publications] Torzilli G: "Accuracy of the preoperative determination of tumor markers in the differentiation of liver mass lesions in surgical patients"Hepatogastroenterology. 49・45. 740-745 (2002)

  • [Publications] Torzilli G: "The vascular control in liver resection : revisitation of a controversial issue. Hepatogastroenterology"Hepatogastroenterology. 49・43. 28-31 (2002)

  • [Publications] Makuuchi M: "Transplantation of organs of the digestive system"Nippon Naika Gakkai Zasshi. 91・2. 566-568 (2002)

  • [Publications] Hayashi S: "Simple technique for repair of complete rectal prolapse using a circular stapler with thiersch procedure"Eur J Surg. 168・2. 124-127 (2002)

  • [Publications] Kasakura Y: "An evaluation of the effectiveness of extended lymph node dissection in patients with gastric cancer: a retrospective study of 1403 cases at a single institution"Journal of surgical research. 103・2. 252-259 (2002)

  • [Publications] Kasakura Y: "Management of perforated gastric carcinoma: a report of 16 cases and review of world literature"The American Surgeon. 68・5. 434-440 (2002)

  • [Publications] Karube H: "E-cadherin expression is inversely proportional to tumor size in experimental liver metastases"Journal of Surgical Research. 106・1. 173-178 (2002)

  • [Publications] Kato K: "In-vitro activity of ciprofloxacin combined with flomoxef against Bacteroides fragilis, compared with that of ciprofloxacin combined with clindamycin"J Infect Chemother. 8・2. 190-193 (2002)

  • [Publications] Mazaki T: "Liposarcoma of the breast : a case report and review of the literature"International Surgery. 87・3. 164-170 (2002)

  • [Publications] Mochizuki F: "Combination chemotherapy comprising 5-fluorouracil, leucovorin, etoposide, and cis-diamminedichloroplatinum for the treatment of advanced gastric cancer"J Cancer Res Clin Oncol. 128・9. 493-496 (2002)

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Published: 2004-04-07   Modified: 2016-04-21  

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