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Isolation and characterization of portal branch ligation-stimulated liver-specific stem cells

Research Project

Project/Area Number 21390375
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionShinshu University

Principal Investigator

MIYAGAWA Shinichi  信州大学, 医学部, 教授 (80229806)

Co-Investigator(Kenkyū-buntansha) MIWA Siroh  信州大学, 医学部, 准教授 (20293516)
MOTOYAMA Hiroaki  信州大学, 医学部附属病院, 助教 (20569587)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Keywords肝臓外科学 / 再生医学 / 門脈結紮(塞栓) / 肝再生 / 組織幹細胞
Research Abstract

We investigated the possibility of isolating hepatic progenitor cells in a portal branch-ligated liver model without administration of any chemical agents. A non-parenchymal cell fraction was prepared from the portal branch-ligated or non-ligated lobe, and seeded onto plates coated with laminin. Most of the cells died, but a small number were able to proliferate. These proliferating cells were cloned as portal branch ligation-stimulated hepatic cells(PBLHCs) by the limiting dilution method. The PBLHCs had a property of stem cells, and differentiated into both hepatocyates and cholangiocytes. In conclusion, successful isolation of bipotent hepatic progenitor cell clones, PBLHCs, from the portal branch-ligated liver lobes of mice provides the possibility of future clinical application of portal vein ligation to induce hepatic progenitor cells.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (25 results)

All 2012 2011 2010 2009

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (6 results)

  • [Journal Article] Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet2012

    • Author(s)
      Akita S, Kubota K, Kobayashi A, Misawa R, Shimizu A, Nakata T, Yokoyama T, Takahashi M, Miyagawa S
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 420(4) Pages: 743-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of gastric gland mucin in preventing gastric cancer in mice2012

    • Author(s)
      Karasawa F, Shiota A, Goso Y, Kobayashi M, Sato Y, Masumoto J, Fujiwara M, Yokosawa S, Muraki T, Miyagawa S, Ueda M, Fukuda MN, Fukuda M, Ishihara K, Nakayama J
    • Journal Title

      J Clin Invest

      Volume: 122(3) Pages: 923-34

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of gastric gland mucin in preventing gastric cancer in mice2012

    • Author(s)
      Karasawa F, Shiota A, Goso Y, Kobayashi M, Sato Y, Masumoto J, Fujiwara M, Yokosawa S, Muraki T, Miyagawa S, Ueda M, Fukuda MN, Fukuda M, Ishihara K, Nakayama J
    • Journal Title

      J Clin Invest

      Volume: 122 Issue: 3 Pages: 923-934

    • DOI

      10.1172/jci59087

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet2012

    • Author(s)
      Akita S, Kobayashi A, Miyagawa S, et al
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 420 Issue: 4 Pages: 743-749

    • DOI

      10.1016/j.bbrc.2012.03.060

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling2011

    • Author(s)
      Arai T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Iinuma N, Iesato Y, Koyama T, Yoshizawa T, Uetake R, Yamauchi A, Yang L, Kawate H, Ogawa S, Kobayashi A, Miyagawa S, Shindo T
    • Journal Title

      Peptides

      Volume: 32(9) Pages: 1855-65

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] COP35, a cholangiocarcinoma-binding oligopeptide, interacts with the clathrin heavy chain accompanied by GRP782011

    • 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

      Volume: 9(6) Pages: 688-701

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological features of hepatitis C virus disease after living donor liver transplantation : relationship with in situ hybridisation data2011

    • 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(2) Pages: 156-60

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling2011

    • Author(s)
      Takuma Arai, Teuhide Koyama, Takayuki Shindo, et al
    • Journal Title

      peptides

      Volume: Volume32(9) Issue: 9 Pages: 1855-65

    • DOI

      10.1016/j.peptides.2011.07.005

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] COP35, a cholangiocarcinoma-bindiag oligopeptide, interacts with the clathrin heavy chain accompanied by GRP782011

    • Author(s)
      Kitahara H, Miyagawa S, et al
    • Journal Title

      Mol Cancer Res

      Volume: 9 Issue: 6 Pages: 688-701

    • DOI

      10.1158/1541-7786.mcr-10-0470

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological features of hepatitis C virus disease after living donor liver transplantation: relationship with in situ hybridisation data2011

    • Author(s)
      Masuda Y, Miyagawa S., et al.
    • Journal Title

      Pathology

      Volume: 43 Pages: 156-160

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation and characterization of portal branch ligation-stimulated Hmga2-positive bipotent hepatic progenitor cells2010

    • 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(3-4) Pages: 298-304

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adrenomedullin in sinusoidal endothelial cells play protective roles against cold injury of liver2010

    • 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(5) Pages: 865-71

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Isolation and characterization of portal branch ligation-stimulated Hmga2-positive bipotent hepatic progenitor cells2010

    • Author(s)
      Sakai H, Motoyama H, Miyagawa S., et al.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 403 Pages: 298-304

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adrenomedullin in sinusoidal endothelial cells play protective roles against cold injury of liver.2010

    • Author(s)
      Iinuma N, Miyagawa S., et al.
    • Journal Title

      Peptides

      Volume: 31 Pages: 865-871

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adrenomedullin in sinusoidal endothelial cells play protective roles against cold injury of liver.2010

    • Author(s)
      Iinuma N, Miyagawa S, Shindo T., et al.
    • Journal Title

      Peptides. 31

      Pages: 865-871

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro reprogramming of adult hepatocytes into insulin-producing cells without viral vectors2009

    • Author(s)
      Motoyama H, Ogawa S, Kubo A, Miwa S, Nakayama J, Tagawa Y, Miyagawa S
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 385(1) Pages: 123-8

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Potential feasibility of early bone marrow cell injection into the spleen for creating functional hepatocytes2009

    • Author(s)
      Misawa R, Soeda J, Ise H, Takahashi M, Kubota K, Mita A, Nakata T, Miyagawa S
    • Journal Title

      Transplantation

      Volume: 87(8) Pages: 1147-54

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Potential feasibility of early bone marrow cell injection into the spleen for creating functional hepatocytes.2009

    • Author(s)
      Misawa R, Miyagawa S., et al.
    • Journal Title

      Transplantation 87

      Pages: 1147-1154

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro reprogramming of adult hepatocytes into insulin-producing cells without viral vectors.2009

    • Author(s)
      Motoyama H, Miyagawa S., et al
    • Journal Title

      Biochem Biophys Res Commun. 385

      Pages: 123-128

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] A Useful Non-viral Procedure to Induce Liver-to-pancreas Reprogramming to Complement Post-operative Pancreatic Endocrine Dysfunction2011

    • Author(s)
      本山博章
    • Organizer
      第17回日本遺伝子治療学会
    • Place of Presentation
      福岡
    • Year and Date
      2011-07-17
    • Related Report
      2011 Final Research Report
  • [Presentation] A Useful Non-viral Procedure to Induce Liver-to-pancreas Reprogramming to Complement Post-operative Pancreatic Endocrine Dysfunction2011

    • Author(s)
      本山博章
    • Organizer
      第17回日本遺伝子治療学会
    • Place of Presentation
      福岡市
    • Year and Date
      2011-07-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Liver-to-pancreas reprogramming膵切除後内分泌機能不全への応用2011

    • Author(s)
      本山博章
    • Organizer
      第66回日本消化器外科学会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-07-15
    • Related Report
      2011 Final Research Report
  • [Presentation] Liver-to-pancreas reprogramming膵切除後内分泌機能不全への応用2011

    • Author(s)
      本山博章
    • Organizer
      第66回日本消化器外科学会
    • Place of Presentation
      名古屋市
    • Year and Date
      2011-07-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] An excellent non-viral procedure to induce liver-to-pancreas reprogramming to complement post-operative pancreatic endocrine dysfunction2010

    • Author(s)
      本山博章
    • Organizer
      8th Catholic International Stem Cell Symposium
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2010-10-02
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Hepatic Portal Branch Ligation-stimulated Appearance of Bipotent Hepatic Progenitor Cells.2009

    • Author(s)
      酒井宏司
    • Organizer
      International society of stem cell research 7^<th> Annual Meeting
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2009-07-08
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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