Explore the hepatic niche: spatiotemporal analyses of mesenchymal stem cells using live imaging technique

• Project/Area Number: 23590966
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: University of Toyama
• Principal Investigator: TAKAHARA Terumi 富山大学, 大学院医学薬学研究部(医学), 准教授 (60240777)
• Co-Investigator(Kenkyū-buntansha): LI Xiao Kan 国立成育医療研究センター, 研究所, 室長 (60321890)
• Co-Investigator(Renkei-kenkyūsha): IKEDA Tomoaki 国立循環器病研究センター, 周産期婦人科部, 部長 (80202894)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 間葉系幹細胞 / イメージング / MMP-9 / ニッチ / 肝再生 / ライブイメージング

Research Abstract

A new and more efficient liver regeneration therapy is required. However, the details of mesenchymal stem cell migration, adhesion, and differentiation into the liver are still unknown as are the efficiency factors for the liver niche. In this study we observed the spatiotemporal dynamics of mesenchymal stem cells that were injected into the spleen and the migration, adhesion, and differentiation of the cells into the liver using multi-photon excitation microscopy. We also analyzed the essential molecules for the liver niche. Mesenchymal stem cells improve liver fibrosis but the stem cells need both their own MMP-9 for migration to the liver and also need to the local MMP-9 for migration and engraftment at the liver. Thus we confirmed that the gradient of both the extracellular matrix and CXCL12 is important.

Research Products

• [Journal Article] 5-aminolevulinic acid combined with ferrous iron enhance the expression of heme oxygenase-1 (2014)
  • Author(s): Nishio Y, et al.
  • Journal Title: Int Immunopharmacol Volume: 19(2) Issue: 2 Pages: 300-307
  • DOI: 10.1016/j.intimp.2014.02.003
  • Peer Reviewed
• [Journal Article] 5-aminolevulinic acid combined with ferrous iron enhance the expression of heme oxygenase-1. (2014)
  • Author(s): Nishio Y, Fujino M, Zhao MY, Ishii T, Ishizuka M, Ito H, Takahashi K, Abe F, Nakajima M, Tanaka T, Taketani S, Nagahara Y, Li Xiao K
  • Journal Title: Int Immunopharmacol. Volume: 19 Pages: 300-307
  • Peer Reviewed
• [Journal Article] Non-myeloablative conditioning is sufficient to induce mixed chimerism and subsequent acceptance of donor specific cardiac and skin grafts (2013)
  • Author(s): Liu C, Zhu P, Saito T, Isaka Y, Nagahara Y, Zhuang J, Li XK
  • Journal Title: Int Immunopharmacol Volume: 16(3) Issue: 3 Pages: 392-8
  • DOI: 10.1016/j.intimp.2013.02.003
  • Peer Reviewed
• [Journal Article] 5-Aminolevulinic acid combined with ferrous iron induces carbon monoxide generation in mouse kidneys and protects from renal ischemia-reperfusion injury (2013)
  • Author(s): Hou J, Cai S, Kitajima Y, Li XK et al
  • Journal Title: Am J Physiol Renal Physiol Volume: 305(8) Issue: 8 Pages: F1149-F1157
  • DOI: 10.1152/ajprenal.00275.2013
  • Peer Reviewed
• [Journal Article] IFN-γdeficiency attenuates hepatic inflammation and fibrosis in a steatohepatitis model induced by a methionine- and choline-deficient high-fat diet (2013)
  • Author(s): Luo XY, Takahara T, Kawai K, Fujino M, Sugiyama T, Tsuneyama K, Tsukada K, Nakae S, Zhong L, Li XK
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 305(12) Issue: 12 Pages: G891-G899
  • DOI: 10.1152/ajpgi.00193.2013
  • Peer Reviewed
• [Journal Article] IFN- deficiency attenuates hepatic inflammation and fibrosis in a steatohepatitis model induced by a methionine and choline-deficient high fat diet. (2013)
  • Author(s): Luo XY, Takahara T, Kawai K, Fujino M, Sugiyama T, Tsuneyama K, Tsukada K, Nakae S, Zhong L, Li Xiao K
  • Journal Title: Am J Physiol Gastrointestinal and Liver Physiol Volume: 305
  • Peer Reviewed
• [Journal Article] Development and treatments of inflammatory cells and cytokines in spinal cord ischemia-reperfusion injury (2013)
  • Author(s): Zhu P, Li JX, Fujino M, Zhuang J, Li Xiao K
  • Journal Title: Mediators Inflamm Volume: 2013 Pages: 701970-701970
  • DOI: 10.1155/2013/701970
  • Peer Reviewed
• [Journal Article] 5-aminolevulinic acid combined with ferrous iron induces carbon monoxide generation in mouse kidneys and protects from renal ischemic-reperfusion injury. (2013)
  • Author(s): Hou J, Cai S, Kitajima Y, Fujino M, Ito H, Takahashi K, Abe F, Tanaka T, Ding Q, Li Xiao K
  • Journal Title: Am J Physiol Renal Physiol Volume: 305
  • Peer Reviewed
• [Journal Article] Non-myeloablative conditioning is sufficient to induce mixed chimerism and subsequent acceptance of donor specific cardiac and skin grafts. (2013)
  • Author(s): Liu C, Zhu P, Saito T, Isaka Y, Nagahara Y, Zhuang J, Li Xiao K
  • Journal Title: Int Immunopharmacol Volume: 16 Pages: 392-8
  • Peer Reviewed
• [Journal Article] Hydrogen-rich University of Wisconsin solution attenuates renal cold ischemia-reperfusion injury. (2012)
  • Author(s): Abe T, Li XK, Yazawa K, Hatayama N, Xie L, Sato B, Kakuta Y, Tsutahara K, Okumi M, Tsuda H, Kaimori JY, Isaka Y, Natori M, Takahara S, Nonomura N.
  • Journal Title: Transplantation. Volume: 94 Issue: 1 Pages: 14-21
  • DOI: 10.1097/tp.0b013e318255f8be
  • Peer Reviewed
• [Journal Article] The role of CD98hc in mouse macrophage functions. (2012)
  • Author(s): Tsumura H, Ito M, Li XK, Nakamura A, Ohnami N, Fujimoto J, Komada H, Ito Y.
  • Journal Title: Cell Immunol. Volume: 276 Issue: 1-2 Pages: 128-34
  • DOI: 10.1016/j.cellimm.2012.04.012
  • Peer Reviewed
• [Journal Article] Deletion of CD98 heavy chain in T cells results in cardiac allograft acceptance by increasing regulatory T cells. (2012)
  • Author(s): Liu Z, Hou J, Chen J, Tsumura H, Ito M, Ito Y, Hu X, Li XK.
  • Journal Title: Transplantation Volume: 93 Issue: 11 Pages: 1116-24
  • DOI: 10.1097/tp.0b013e31824fd7cd
  • Peer Reviewed
• [Journal Article] Bone marrow-derived conventional, but not cloned, mesenchymal stem cells suppress lymphocyte proliferation and prevent graft-versus-host disease in rats. (2012)
  • Author(s): Kitazawa Y, Li XK, Xie L, Zhu P, Kimura H, Takahara S.
  • Journal Title: Cell Transplant. Volume: 21 Issue: 2-3 Pages: 581-90
  • DOI: 10.3727/096368911x605510
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase-9 contributes to the (2012)
  • Author(s): Kawai K., Xue F., Takahara T., Kudo H., Yata Y., Zhang W. and Sugiyama T.
  • Journal Title: Cell Transplant Volume: 21 Issue: 2-3 Pages: 453-464
  • DOI: 10.3727/096368911x605367
  • Peer Reviewed
• [Journal Article] Theaflavin attenuates ischemia-reperfusion injury in a mouse fatty liver model (2012)
  • Author(s): Luo XY, Takahara T, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 417(1) Issue: 1 Pages: 287-93
  • DOI: 10.1016/j.bbrc.2011.11.102
  • Peer Reviewed
• [Journal Article] Comparison of lafutidine and rabeprazole in 7-day second-line amoxicillin- and tronidazole-containing triple therapy for (2012)
  • Author(s): Kudo T., Fujinami H., Ando T., Nishikawa J., Ogawa K., Hosokawa A., Orihara T., Murakami J., Takahara T. and Sugiyama T
  • Journal Title: Helicobacter Volume: 17 Issue: 4 Pages: 277-281
  • DOI: 10.1111/j.1523-5378.2012.00943.x
  • Peer Reviewed
• [Journal Article] Identification of a novel biomarker gene set with sensitivity and specificity for distinguishing between allograft rejection and tolerance. (2012)
  • Author(s): Xie L, Ichimaru N, Morita M, Chen J, Zhu P, Wang J, Urbanellis P, Shalev I, Nagao S, Sugioka A, Zhong L, Nonomura N, Takahara S, Levy GA, Li XK.
  • Journal Title: Liver Transpl Volume: 18 Issue: 4 Pages: 444-54
  • DOI: 10.1002/lt.22480
  • Peer Reviewed
• [Journal Article] A novel Y231del mutation of HFE in hereditary haemochromatosis provides in vivo evidence that the Huh-7 is a human haemochromatotic cell line. (2011)
  • Author(s): Takano A, Niimi H, et al.
  • Journal Title: Liver Int Volume: 31 Issue: 10 Pages: 1593-1597
  • DOI: 10.1111/j.1478-3231.2011.02620.x
  • Peer Reviewed
• [Journal Article] A case of adult-onset type II citrullinemia induced by hospital diet. (2011)
  • Author(s): Ueda A, Okada K, et al.
  • Journal Title: Clin J Gastroenterol Volume: 4 Issue: 1 Pages: 28-33
  • DOI: 10.1007/s12328-010-0188-3
  • Peer Reviewed
• [Presentation] IFN-γdeficiency attenuates hepatic inflammation and fibrosis in mouse steatohepatitis (2013)
  • Author(s): Takahara T
  • Organizer: The 17^<th> International Society of Hepatic Sinusoidal Research and 27^<th> Annual Meeting for Hepatic Sinusoidal Reseach Japan
  • Place of Presentation: Osaka
• [Presentation] 6) IFN-γ deficiency attenuates hepatic inflammation and fibrosis in mouse steatohepatitis. (2013)
  • Author(s): Takahara T
  • Organizer: 17th ISHSR & 27th HSRJ
  • Place of Presentation: Osaka
• [Presentation] IFN-γdeficiency attenuates hepatic inflammation and fibrosis in a steatohepatitis model induced by a methionine- and choline-deficient high-fat diet (2012)
  • Author(s): Luo XY, Takahara T, et al
  • Organizer: The 63th Annual Meeting of the America Association for the Study of Liver Disease
  • Place of Presentation: Boston
• [Presentation] MMP-9 promotes the trafficking of transplanted bone marrow cells that attenuates hepatic fibrosis in chronic CCl4 liver injury (2012)
  • Author(s): Kawai K, Takahara T, et al
  • Organizer: The 10^<th> Annual Meeting of International Society for Stem Cell Research
  • Place of Presentation: Yokohama
• [Presentation] MMP-9 ptomotes the trafficking of transplanted (2012)
  • Author(s): Kawai K., Luo X., Tsukada K., SugiyamaT. and Takahara T
  • Organizer: ISSCR 10th Annual Meeting
  • Place of Presentation: Yokohama
• [Presentation] IFN-g deficiency attenuates hepatic inflammation (2012)
  • Author(s): Luo, X., Takahara T., Kawai K., Tsukada K. and Li X.
  • Organizer: The 63rd Annual Meeting of the American Association for the Study of Liver Disease
  • Place of Presentation: Boston, USA
• [Presentation] Theaflavin attenuates ischemia-reperfusion injury in a mouse fatty liver model (2011)
  • Author(s): Luo XY, Takahara T, et al
  • Organizer: The 10^<th> International Society of Hepatic Sinusoidal Research
  • Place of Presentation: Florence
• [Presentation] Magic-Factor, a partial agonist of Met, act as a safe hepatotrophic cytokine (2011)
  • Author(s): Takahara T, Kawai K et al
  • Organizer: The 62th Annual Meeting of the America Association for the Study of Liver Disease
  • Place of Presentation: San Francisco
• [Presentation] Magic-Factor, a partial agonist of Met, acts as a safe hepatotrophic cytokine (2011)
  • Author(s): Takahara T, Kawai K, et al.
  • Organizer: The 62th Annual Meeting of the American Association for the Study of Liver Diseases.
  • Place of Presentation: San Francisco
• [Presentation] Theaflavin attenuates ischemia/reperfusion injury in mouse fatty liver model. (2011)
  • Author(s): Luo XY, Takahara T, et al.
  • Organizer: The 16th International Society for Hepatic Sinusoidal Research.
  • Place of Presentation: Florence
• [Book] B型肝炎の診療を極める (2013)
  • Author(s): 高原照美
  • Total Pages: 160
  • Publisher: 文光堂
• [Book] 消化器病学 (2013)
  • Author(s): 高原照美、高野敦子
  • Total Pages: 1234
  • Publisher: 西村書店
• [Book] 病気の分子形態学 (2011)
  • Author(s): 高原照美
  • Total Pages: 370
  • Publisher: 学際企画
• [Book] 病気の分子形態学 (2011)
  • Author(s): 高原照美
  • Total Pages: 370
  • Publisher: 学祭企画