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

• Project/Area Number: 21390375
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Shinshu 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: ¥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.

Research Products

• [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 diet (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Essential role of gastric gland mucin in preventing gastric cancer in mice (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Essential role of gastric gland mucin in preventing gastric cancer in mice (2012)
  • 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
  • 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 diet (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling (2011)
  • 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
  • Peer Reviewed
• [Journal Article] COP35, a cholangiocarcinoma-binding oligopeptide, 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 Volume: 9(6) Pages: 688-701
  • 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 Volume: 43(2) Pages: 156-60
  • Peer Reviewed
• [Journal Article] Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling (2011)
  • 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
  • Peer Reviewed
• [Journal Article] COP35, a cholangiocarcinoma-bindiag oligopeptide, interacts with the clathrin heavy chain accompanied by GRP78 (2011)
  • 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
  • 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, Miyagawa S., et al.
  • Journal Title: Pathology Volume: 43 Pages: 156-160
  • 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(3-4) Pages: 298-304
  • 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(5) Pages: 865-71
  • Peer Reviewed
• [Journal Article] Isolation and characterization of portal branch ligation-stimulated Hmga2-positive bipotent hepatic progenitor cells (2010)
  • Author(s): Sakai H, Motoyama H, Miyagawa S., et al.
  • Journal Title: Biochem Biophys Res Commun. Volume: 403 Pages: 298-304
  • 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
  • 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
  • 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 Volume: 385(1) Pages: 123-8
  • 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 Volume: 87(8) Pages: 1147-54
  • 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
  • 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
  • Peer Reviewed
• [Presentation] A Useful Non-viral Procedure to Induce Liver-to-pancreas Reprogramming to Complement Post-operative Pancreatic Endocrine Dysfunction (2011)
  • 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
• [Presentation] A Useful Non-viral Procedure to Induce Liver-to-pancreas Reprogramming to Complement Post-operative Pancreatic Endocrine Dysfunction (2011)
  • 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
• [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
• [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
• [Presentation] An excellent non-viral procedure to induce liver-to-pancreas reprogramming to complement post-operative pancreatic endocrine dysfunction (2010)
  • Author(s): 本山博章
  • Organizer: 8th Catholic International Stem Cell Symposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-10-02
• [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