New therapeutic approach with bone marrow cell for hereditary liver diseases

• Project/Area Number: 20591604
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Shinshu University
• Principal Investigator: NAKATA Takenari Shinshu University, 医学部附属病院, 講師 (70377638)
• Co-Investigator(Kenkyū-buntansha): MIYAGAWA Shinichi 信州大学, 医学部, 教授 (80229806) ; MOTOYAMA Hiroaki 信州大学, 医学部附属病院, 助教(特定雇用) (20569587) ; 三輪 史郎 信州大学, 医学部, 准教授 (20293516)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 移植医療 / 再生医療 / 骨髄移植 / 移植・再生医療 / 骨髄細胞

Research Abstract

We used Long Evans Cinnamon (LEC) rats as recipients, a model of Wilson disease and liver carcinogenesis. GFP-expressing BMCs were injected into newborn LEC rats through the spleen.
At 18 months after injection, we found some green fluorescent protein-expressing areas macroscopically in the liver of treated LEC rats. The oxidative activity of ceruloplasmin increased. Moreover, we confirmed that the BMDHs were generated by cell fusion and was not detected in any of the neoplastic lesions or cholngiofibrotic regions.
Our results suggest that this novel strategy for creating BMDHs is effective and safe.

Research Products

• [Journal Article] COP35, a cholangiocarcinoma-binding oligo-peptide, interacts with the clathrin heavy chain accompanied by GRP78. (2011)
  • Author(s): Kitahara H, Masumoto J, Parker AL, Maruta F, Kubo N, Shimizu A, Akita N, Miwa S, Kobayashi N, Nakayama J, Miyagawa S.
  • Journal Title: Mol Cancer Res. in press
  • Peer Reviewed
• [Journal Article] Clinicopathological features of hepatitis C virus disease after living donor liver transplantation : relationship with in situ hybridisation data. (2011)
  • Author(s): Masuda Y, Nakazawa Y, Matsuda K, Sano K, Mita A, Ohno Y, Urata K, Ikegami T, Miwa S, Miyagawa S.
  • Journal Title: Pathology. 43 Pages: 156-160
  • Peer Reviewed
• [Journal Article] Noncompliance with medications in pediatric patients after living-donor liver transplantation. (2010)
  • Author(s): Masuda Y, Mita A, Ohno Y, Urata K, Nakazawa Y, Ikegami T, Masaru T, Miyagawa S.
  • Journal Title: Transplant Proc. 42 Pages: 4191-4192
  • Peer Reviewed
• [Journal Article] Isolation and characterization of portal branch ligation-stimulated Hmga2-positive bipotent hepatic progenitor cells. (2010)
  • Author(s): Sakai H, Tagawa Y, Tamai M, Motoyama H, Ogawa S, Soeda J, Nakata T, Miyagawa S.
  • Journal Title: Biochem Biophys Res Commun. 17;403 Pages: 298-304
  • Peer Reviewed
• [Journal Article] Induction of high endothelial venule-like vessels expressing GlcNAc6ST-1-mediated L-selectin ligand carbohydrate and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in a mouse model of "Candidatus Helicobacter heilmannii"-induced gastritis and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. (2010)
  • Author(s): Suzuki A, Kobayashi M, Matsuda K, Matsumoto T, Kawakubo M, Kumazawa S, Koide N, Miyagawa S, Ota H.
  • Journal Title: Helicobacter. 15 Pages: 538-548
  • Peer Reviewed
• [Journal Article] Disease recurrence patterns after R0 resection of hilar cholangiocarcinoma. (2010)
  • Author(s): Kobayashi A, Miwa S, Nakata T, Miyagawa S.
  • Journal Title: Br J Surg. 97(1) Pages: 56-64
  • Peer Reviewed
• [Journal Article] Adrenomedullin in sinusoidal endothelial cells play protective roles against cold injury of liver. (2010)
  • Author(s): Iinuma N, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Arai T, Yoshizawa T, Koyama T, Uetake R, Kawate H, Muto S, Tagawa Y, Miyagawa S, Shindo T.
  • Journal Title: Peptides. 31 Pages: 865-871
  • Peer Reviewed
• [Journal Article] Isolation and characterization of portal branch ligation-stimulated Hmga2-positive bipotent hepatic progenitor cells. (2010)
  • Author(s): Sakai H, Tagawa Y, Tamai M, Motoyama H, Ogawa S, Soeda J, Nakata T, Miyagawa S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 403 Pages: 298-304
  • Peer Reviewed
• [Journal Article] 膵癌の治療:膵癌の外科治療の現況と最近の化学療法 (2010)
  • Author(s): 中田岳成
  • Journal Title: 信州医学会雑誌 Volume: 58 Pages: 95-102
  • Peer Reviewed
• [Journal Article] Disease recurrence patterns after RO resection of hilar cholangiocarcinoma. (2010)
  • Author(s): Kobayashi A, Miwa S, Nakata T, Miyagawa S.
  • Journal Title: Br J Surg. Volume: 97 Pages: 56-64
  • Peer Reviewed
• [Journal Article] Adrenomedullin in sinusoidal endothelial cells play protective roles against cold injury of liver. (2010)
  • Author(s): Iinuma N, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Arai T, Yoshizawa T, Koyama T, Uetake R, Kawate H, Muto S, Tagawa Y, Miyagawa S, Shindo T
  • Journal Title: Peptides. Volume: 31 Pages: 865-871
  • Peer Reviewed
• [Journal Article] Advances in therapeutics for liver metastasis from colorectal cancer. (2010)
  • Author(s): Kobayashi A, Miyagawa S.
  • Journal Title: World J Gastrointest Oncol. Volume: 2 Pages: 380-389
  • Peer Reviewed
• [Journal Article] Clinicopathological features of hepatitis C virus disease after living donor liver transplantation : relationship with in situ hybridisation data. (2010)
  • Author(s): Masuda Y, Nakazawa Y, Matsuda K, Sano K, Mita A, Ohno Y, Urata K, Ikegami T, Miwa S, Miyagawa S.
  • Journal Title: Pathology Volume: 43 Pages: 156-160
  • Peer Reviewed
• [Journal Article] Noncompliance with medications in pediatric patients after living-donor liver transplantation. (2010)
  • Author(s): Masuda Y, Mita A, Ohno Y, Urata K, Nakazawa Y, Ikegami T, Masaru T, Miyagawa S.
  • Journal Title: Transplant Proc. Volume: 42 Pages: 4191-4192
  • Peer Reviewed
• [Journal Article] Disease recurrence patterns after R0 resection of hilar cholangiocarcinoma. (2010)
  • Author(s): Kobayashi A, Miwa S, Nakata T, Miyagawa S.
  • Journal Title: Br J Surg 97 Pages: 56-64
  • Peer Reviewed
• [Journal Article] In vitro reprogramming of adult hepatocytes into insulin-producing cells without viral vectors. (2009)
  • Author(s): Motoyama H, Ogawa S, Kubo A, Miwa S, Nakayama J, Tagawa Y, Miyagawa S.
  • Journal Title: Biochem Biophys Res Commun. 385(1) Pages: 123-128
  • Peer Reviewed
• [Journal Article] Potential feasibility of early bone marrow cell injection into the spleen for creating functional hepatocytes. (2009)
  • Author(s): Misawa R, Soeda J, Ise H, Takahashi M, Kubota K, Mita A, Nakata T, Miyagawa S.
  • Journal Title: Transplantation. 87 Pages: 1147-1154
  • Peer Reviewed
• [Journal Article] Clinical and pathological features of primary carcinoma of the cystic duct. (2009)
  • Author(s): Nakata T, Kobayashi A, Miwa S, Soeda J, Uehara T, Miyagawa S.
  • Journal Title: J Hepatobiliary Pancreat Surg. 16 Pages: 75-82
  • NAID: 10025137871
  • Peer Reviewed
• [Journal Article] Administration of dalteparin based on the activated clotting time for prophylaxis of hepatic vessel thrombosis in living donor liver transplantation. (2009)
  • Author(s): Uchikawa Y, Ikegami T, Masuda Y, Ohno Y, Mita A, Urata K, Nakazawa Y, Terada M, Miyagawa S.
  • Journal Title: Transplant Proc. 41 Pages: 3784-3790
  • Peer Reviewed
• [Journal Article] Prognosis of adult patients transplanted with liver grafts < 35% of their standard liver volume. (2009)
  • Author(s): Ikegami T, Masuda Y, Ohno Y, Mita A, Kobayashi A, Urata K, Nakazawa Y, Miwa S, Hashikura Y, Miyagawa S.
  • Journal Title: Liver Transpl. 15 Pages: 1622-1630
  • Peer Reviewed
• [Journal Article] Potential feasibility of early bone marrow cell injection into the spleen for creating functional hepatocytes. (2009)
  • Author(s): Misawa R, Soeda J, Ise H, Takahashi M, Kubota K, Mita A, Nakata T, Miyagawa S.
  • Journal Title: Transplantation 87 Pages: 1147-1154
  • Peer Reviewed
• [Journal Article] Clinical and pathological features of primary carcinoma of the cystic duct. (2009)
  • Author(s): Nakata T, Kobayashi A, Miwa S, Soeda J, Uehara T, Miyagawa S.
  • Journal Title: J Hepatobillary Pancreat Surg 16 Pages: 75-82
  • NAID: 10025137871
  • Peer Reviewed
• [Journal Article] Purification method using iodixanol (OptiPrep)-based density gradient significantly reduces cytokine chemokine production from human islet preparations, leading to prolonged beta-cell survival during pretransplantation culture. (2009)
  • Author(s): Mita A, Ricordi C, Miki A, Barker S, Khan A, Alvarez A, Hashikura Y, Miyagawa S, Ichii H.
  • Journal Title: Transplant Proc 41 Pages: 314-5
  • Peer Reviewed
• [Journal Article] A case of well-differentiated cholangiolocellular carcinoma visualized with contrast-enhanced ultrasonography using Sonazoid. (2009)
  • Author(s): Joshita S, Ichijo T, Suzuki F, Yokoyama T, Sugiyama Y, Fukushima M, Kamijo A, Komatsu M, Umemura T, Yoshizawa K, Miyagawa S, Tanaka E.
  • Journal Title: Hepatol Res. 39 Pages: 207-12
  • Peer Reviewed
• [Journal Article] Prognostic impact of anatomical resection on early and late intrahepatic recurrence in patients with hepatocellular carcinoma. (2008)
  • Author(s): Kobayashi A, Miyagawa S, Miwa S, Nakata T.
  • Journal Title: J Hepatobiliary Pancreat Surg. 15 Pages: 515-521
  • NAID: 10024305908
  • Peer Reviewed
• [Journal Article] Identification of genes associated with multiple nodules in hepatocellular carcinoma using cDNA microarray: multicentric occurrence or intrahepatic metastasis? (2008)
  • Author(s): Nakata T, Seki N, Miwa S, Kobayashi A, Soeda J, Nimura Y, Kawasaki S, Miyagawa S.
  • Journal Title: Hepatogastroenterology. 55 Pages: 865-872
  • Peer Reviewed
• [Journal Article] Primary liver carcinoma exhibiting dual hepatocellular-biliary epithelial differentiations associated with citrin deficiency. (2008)
  • Author(s): Soeda J, Yazaki M, Nakata T, Miwa S, Ikeda S, Hosoda W, Iijima M, Kobayashi K, Saheki T, Kojiro M, Miyagawa S.
  • Journal Title: J Clin Gastroenterol. 42 Pages: 855-860
  • Peer Reviewed
• [Journal Article] Identification of genes associated with multiple nodules in hepatocellular carcinoma using cDNA microarray : multicentric occurrence or intrahepatic metastasis? (2008)
  • Author(s): Nakata T, Kobayashi A, Miwa S, Soeda J, Uehara T, Miyagawa S.
  • Journal Title: Hepatogastroenterology. 55 Pages: 865-72
  • Peer Reviewed
• [Journal Article] Bone marrowderived cells fuse with hepatic oval cells but are not invol ved in hepatic tumorigenesis in the choline-deficient ethiordne-supplemented diet rat model. (2008)
  • Author(s): Kubota K, Soeda J, Misawa R, Mihara M, Miwa S, Ise H, Takahashi M, Miyagawa S.
  • Journal Title: Carcinogenesis. 29 Pages: 448-54
  • Peer Reviewed
• [Journal Article] Anti-proinflammatory effects of sirolimus on human islet preparations. (2008)
  • Author(s): Mita A, Ricordi C, Miki A, Barker S, Haertter R, Hashikura Y, Miyagawa S, Burke GW 3rd, Inverardi L, Ichii H.
  • Journal Title: Transplantation. 86 Pages: 46-53
  • Peer Reviewed
• [Journal Article] Identification of oligopeptide binding to colon cancer cells separated from patients using laser capture microdissection. (2008)
  • Author(s): Kubo N, Akita N, Shimizu A, Kitahara H, Parker AL, Miyagawa S.
  • Journal Title: J Drug Target 16 Pages: 396-404
  • Peer Reviewed
• [Journal Article] NADPH oxidase 1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor expression. (2008)
  • Author(s): Komatsu D, Kato M, Nakayama J, Miyagawa S, Kamata T.
  • Journal Title: Oncogene. 27 Pages: 4724-32
  • Peer Reviewed
• [Journal Article] Primary liver carcinoma exhibiting dual hep atocellularbiliary epithelial differentiations associated with citrin deficiency. (2008)
  • Author(s): Soeda J, Yazaki M, Nakata T, Miwa S, Ikeda S, Hosoda W, Iijima M, Kobayashi K, Saheki T, Kojiro M, Miyagawa S.
  • Journal Title: J Clin Gastroenterol. 42 Pages: 855-60
  • Peer Reviewed
• [Journal Article] Arterial reconstruction in a case of subintimal dissection of celiac arterial tributaries in living donor liver transplantation. (2008)
  • Author(s): Ikegami T, Masuda Y, Ohno Y, Urata K, Nakazawa Y, Miwa S, Hashikura Y Miyagawa S.
  • Journal Title: Transplant Proc 40 Pages: 3794-6
  • Peer Reviewed
• [Journal Article] Prognostic impact of anatomical resection on early and late intrahepaticrecurrence in patients with hepatocellular carcinoma. (2008)
  • Author(s): Kobayashi A, Miyagawa S, Miwa S, Nakata T.
  • Journal Title: Hepatobiliary Pancreat Surg. 15 Pages: 515-21
  • Peer Reviewed
• [Presentation] 胆道癌取扱い規約におけるCalot三角、胆嚢管の扱いを考える (2010)
  • Author(s): 中田岳成
  • Organizer: 第18回日本消化器関連学会週間
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-15
• [Presentation] 胆道癌取扱い規約におけるCalot三角, 胆嚢管の扱いを考える (2010)
  • Author(s): 中田岳成
  • Organizer: 第18回日本消化器関連学会週間
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2010-10-15
• [Presentation] An excellent non-viral procedure to induce liver-to-pancreas reprogramming to complement post-operative pancreatic endocrine dysfunction (2010)
  • Author(s): Hiroaki Motoyama
  • Organizer: 8th Catholic International Stem Cell Symposium
  • Place of Presentation: Korea
  • Year and Date: 2010-10-02
• [Presentation] An excellent non-viral procedure to induce liver-to-pancreas reprogramming to complement post-operative pancreatic endocrine dysfunction. (2010)
  • Author(s): Hiroaki Motoyama
  • Organizer: 8th Catholic International Stem Cell Symposium
  • Place of Presentation: Catholic University of Korea
  • Year and Date: 2010-10-02
• [Presentation] 膵癌切除症例に対する術後補助化学療法(gemcitabine)の課題 (2010)
  • Author(s): 中田岳成
  • Organizer: 第65回日本消化器外科学会総
  • Place of Presentation: 下関市
  • Year and Date: 2010-07-15
• [Presentation] 膵癌切除症例に対する術後補助化学療法(gemcitabine)の課題 (2010)
  • Author(s): 中田岳成
  • Organizer: 第65回日本消化器外科学会総会
  • Place of Presentation: 下関市民会館
  • Year and Date: 2010-07-15
• [Presentation] 膵癌切除後GEM術後補助化学療法施行症例の再発診断 (2009)
  • Author(s): 中田岳成
  • Organizer: 第64回日本消化器外科学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-18
• [Presentation] 膵癌切除後GEM術後補助化学療法施行症例の再発診断 (2009)
  • Author(s): 中田岳成
  • Organizer: 第64回 日本消化器外科学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-07-18
• [Presentation] 膵癌切除例に対する術後補助化学療法、再発時S-1療法の治療成績 (2009)
  • Author(s): 中田岳成
  • Organizer: 第109回日本外科学会
  • Place of Presentation: 福岡
  • Year and Date: 2009-04-04
• [Presentation] 膵癌切除例に対する術後補助化学療法,再発時S-1療法の治療成績 (2009)
  • Author(s): 中田岳成
  • Organizer: 第109回 日本外科学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2009-04-04
• [Presentation] 非閉塞性黄疸胆嚢癌症例に対する胆管切除付加の意義 (2008)
  • Author(s): 中田岳成
  • Organizer: 第63回日本消化器外科学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-17
• [Presentation] 肝門部胆管癌における胆管切除断端と予後の検討 (2008)
  • Author(s): 三輪史郎
  • Organizer: 第63回日本消化器外科学会
  • Place of Presentation: 札幌市教育文化会館
  • Year and Date: 2008-07-17
• [Presentation] 非閉塞性黄疸胆嚢癌症例に対する胆管切除付加の異議 (2008)
  • Author(s): 中田岳成
  • Organizer: 第63回日本消化器外科学会
  • Place of Presentation: 札幌北海道厚生年金会館
  • Year and Date: 2008-07-16
• [Presentation] 膵癌切除例に対する術後補助化学療法および再発時S-1上乗せ療法の治療成績 (2008)
  • Author(s): 中田岳成
  • Organizer: 第20回日本肝胆膠外科学会
  • Place of Presentation: 山形国際ホテル
  • Year and Date: 2008-05-30
• [Presentation] 肝膵同時切除術の周術期成績向上を目指して (2008)
  • Author(s): 三輪史郎
  • Organizer: 第20回日本肝胆膵外科学会
  • Place of Presentation: 山形国際ホテル
  • Year and Date: 2008-05-29
• [Presentation] 膵癌切除例に対する術後補助化学療法および再発時治療の成績 (2008)
  • Author(s): 中田岳成
  • Organizer: 第108回日本外科学会
  • Place of Presentation: 長崎ブリックホテル
  • Year and Date: 2008-05-17
• [Presentation] 肝門部胆管癌における再発時期と予後因子の検討 (2008)
  • Author(s): 三輪史郎
  • Organizer: 第108回日本外科学会
  • Place of Presentation: ベストウェスタンプレミアムホテル長崎
  • Year and Date: 2008-05-15
• [Book] 肝疾患クリニカルスタンダード (2010)
  • Author(s): 中田岳成
  • Publisher: (株)文光堂