Fibrinolytic factors control MSC expansion thereby enhancing hematopoiesis

• Project/Area Number: 16K09821
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: Heissig Beate 東京大学, 医科学研究所, 准教授 (30372931)
• Research Collaborator: Hattori Koichi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 間葉系幹細胞 / stem cells / mesenchymal stem cells / fibrinolytic factors / hematopoiesis / 幹細胞

Outline of Final Research Achievements

Tissue plasminogen activator (tPA) is an enzyme used for the treatment of stroke patients. Mesenchymal stem cells can expand stem cells in various tissues, including the tumor bed. We show that tPA can expand mesenchymal stem cells within the bone marrow and the tumor cell bed. We propose that controlling tPA levels can regulate hematopoietic stem cell expansion and tumor cell growth.

Academic Significance and Societal Importance of the Research Achievements

骨髄および腫瘍細胞ニッチにおけるＭＳＣの動員または拡大を調節することにおける線維素溶解因子の重要な役割を強調している。造血幹細胞ならびに癌幹細胞の増殖におけるＭＳＣの役割を実証する研究と一緒に、我々は、線維素溶解因子が臨床現場での造血幹細胞の増殖に有用であり得ることを提案する。 ＭＳＣを動員するそれらの能力のために癌患者に与えられる線維素溶解因子は、腫瘍細胞増殖を支持するかもしれない。

Research Products

• [Journal Article] The fibrinolytic factor tPA drives LRP1-mediated melanoma growth and metastasis (2019)
  • Author(s): Salama Y, Lin SY, Dhahri D, Hattori K, Heissig B
  • Journal Title: FASEB J Volume: 33 Issue: 3 Pages: 3465-3480
  • DOI: 10.1096/fj.201801339rrr
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The angiogenic factor Egfl7 alters thymogenesis by activating Flt3 signaling (2017)
  • Author(s): Salama Yousef、Hattori Koichi、Heissig Beate
  • Journal Title: Biochem Biophys Res Commun Volume: 490 Issue: 2 Pages: 209-216
  • DOI: 10.1016/j.bbrc.2017.06.023
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The role of plasmin in the pathogenesis of murine multiple myeloma (2017)
  • Author(s): Eiamboonsert S, Salama Y, Watarai H, Dhahri D, Tsuda Y, Okada Y, Hattori K, Heissig B.
  • Journal Title: Biochem Biophys Res Commun. Volume: 488 Issue: 2 Pages: 387-392
  • DOI: 10.1016/j.bbrc.2017.05.062
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pharmacological targeting of plasmin prevents lethality and tissue damage in a murine model of macrophage activation syndrome (2017)
  • Author(s): 1.Shimazu H, Munakata S, Tashiro Y, Salama Y, Eiamboonser S, Ohta Y, Onoda H, Tsuda Y, Okada Y, Nakauchi H, Heissig B and Hattori K
  • Journal Title: Blood Volume: 印刷中 Issue: 1 Pages: 59-72
  • DOI: 10.1182/blood-2016-09-738096
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice. (2017)
  • Author(s): Honjo K, Shinya Munakata S, Tashiro Y, Salama Y, Shimazu H, Eiamboonsert S, Dhahri D, Ichimura A, Dan T, Miyata T, Takeda K, Sakamoto K, Hattori K, Heissig B.
  • Journal Title: FASEB J Volume: 31 Pages: 2625-2637
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice. (2017)
  • Author(s): Honjo K, Munakata S, Tashiro Y, Salama Y, Shimazu H, Eiamboonsert S, Dhahri D, Ichimura A, Dan T, Miyata T, Takeda K, Sakamoto K, Hattori K, Heissig B.
  • Journal Title: FASEB Journal Volume: - Issue: 6 Pages: 2625-2637
  • DOI: 10.1096/fj.201600871rr
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells (2016)
  • Author(s): Dhahri D, Sato-Kusubata K, Ohki-Koizumi M, Nishida C, Tashiro Y, Munakata S, Shimazu H, Salama Y, Eiamboonsert S, Nakauchi H, Hattori K and Heissig B
  • Journal Title: Blood Volume: 128 Pages: 1063-75
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Niche cells for tissue regeneration (2018)
  • Author(s): Beate Heissig
  • Organizer: Joint Workshop between Norway and Japan in Regenerative Medicine
  • Invited
• [Presentation] Dual or half career: trapped between success and support. (2018)
  • Author(s): Heissig Beate
  • Organizer: European Research Nights
  • Int'l Joint Research / Invited
• [Presentation] Fibrinolytic factors conrols MSC expansion (2018)
  • Author(s): Salama Yousef, Heissig Beate
  • Organizer: 平成29年度先端モデル動物支援プラットフォーム成果発表会
• [Presentation] 1.The niche/microenvrionment shapes the fate of researchers and stem cells (2016)
  • Author(s): Heissig Beate
  • Organizer: European Research Day
  • Place of Presentation: Delegation of the European Union to Japan, Tokyo
  • Invited
• [Presentation] Fibrinolytic factors in stem cell regulation and cancer (2016)
  • Author(s): Heissig Beate
  • Organizer: The 91th of Stem Cell Biology and Regenerative Medicine Forum
  • Place of Presentation: 東京大学医科学研究所（東京都港区）
  • Int'l Joint Research / Invited