Technology to Regulate Stem Cell Functions via Dynamic Modulations of Microenvironments

• Project/Area Number: 17H00855
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Kyoto University
• Principal Investigator: Tanaka Motomu 京都大学, 高等研究院, 特任教授 (00706814)
• Co-Investigator(Kenkyū-buntansha): 吉川 洋史 埼玉大学, 理工学研究科, 教授 (50551173)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥43,550,000 (Direct Cost: ¥33,500,000、Indirect Cost: ¥10,050,000); Fiscal Year 2019: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000); Fiscal Year 2018: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000); Fiscal Year 2017: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
• Keywords: バイオメカニクス / 幹細胞制御 / 細胞微小環境モデル / 細胞接着 / 細胞変形・遊走 / 細胞バイオメカニクス

Outline of Final Research Achievements

This project aims to develop novel technological platforms to understand the adaptation mechanism of human stem cells to dynamic environmental changes as well as to control their differentiation and self-renewal. We succeeded in the establishment of unique measurement techniques and analytical tools specifically designed for three target systems: (1) chemical cues that control adhesion and migration of hman hematopoietic stem cells in bone marrow microenvironments, (2) physical cues that control proliferation of human mesenchymal stem cells, and (3) cell adhesion that regulates functions of human indiced pluripotent stem cells cells.

Academic Significance and Societal Importance of the Research Achievements

学術的成果として特筆すべきものは、精密に設計した骨髄微小環境モデルを駆使して、臨床薬や骨髄内ケモカインがヒト造血幹細胞の接着強度や遊走へ与える影響を精密計測、その解析結果を数値指標化することで、「化学的刺激を受けた造血幹細胞の運動方程式」を確立したことがあげられる。この成果がもたらす社会的意義としては、急性骨髄性白血病などの治療において、標的阻害剤や化学療法による未知の副作用を定量的に記録する共通プラットフォームが確立されたことが大きな成果として挙げられる。

Research Products

• [Int'l Joint Research] Heidelberg University(ドイツ)
• [Int'l Joint Research] Heidelberg University/Dusseldorf University(ドイツ)
• [Int'l Joint Research] ESRF(フランス)
• [Int'l Joint Research] Heidelberg University/Medical Faculty Mannheim(ドイツ)
• [Int'l Joint Research] ESRF/Institut Curie(フランス)
• [Journal Article] A physical biomarker of the quality of cultured corneal endothelial cells and of the long-term prognosis of corneal restoration in patients. (2019)
  • Author(s): Yamamoto, A.; Tanaka, H.; Toda, M.; Sotozono, C.; Hamuro, J.; Kinoshita, S.; Ueno, M. & Tanaka, M.
  • Journal Title: Nat. Biomed. Eng. Volume: 3 Issue: 12 Pages: 953-960
  • DOI: 10.1038/s41551-019-0429-9
  • Peer Reviewed
• [Journal Article] Dynamic Contact Guidance of Myoblasts by Feature Size and Reversible Switching of Substrate Topography: Orchestration of Cell Shape, Orientation, and Nematic Ordering of Actin Cytoskeletons. (2019)
  • Author(s): Linke, P.; Suzuki, R.; Yamamoto, A.; Nakahata, M.; Kengaku, M.; Fujiwara, T.; Ohzono, T. & Tanaka, M.
  • Journal Title: Langmuir Volume: 35 Pages: 7538-7551
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dynamic cellular phynotyping defines specific mobilization mechanisms of human hematopoietic stem and progenitor cells induced by SDF1α versus synthetic agents. (2018)
  • Author(s): Monzel, C.; Becker, A. S.; Saffrich, R.; Wuchter, P.; Eckstein, V.; Ho, A. D.* & Tanaka, M.*
  • Journal Title: Scientific Reports Volume: 8:1841 Issue: 1 Pages: 1-10
  • DOI: 10.1038/s41598-018-19557-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Simple physical model unravels influences of chemokine on shape deformation and migration of human hematopoietic stem cells. (2018)
  • Author(s): Ohta, T.; Monzel, C.; Becker, A. S.; Ho, A. D. & Tanaka, M.
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 10630-10630
  • DOI: 10.1038/s41598-018-28750-x
  • NAID: 120006529719
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells. (2018)
  • Author(s): Yu, L.; Li, J.; Hong, J.; Takashima, Y.; Fujimoto, N.; Nakajima, M.; Yamamoto, A.; Dong, X.; Dang, Y.; Hou, Y.; Yang, W.; Minami, I.; Okita, K.; Tanaka, M.; Luo, C.; Tang, F.; Chen, Y.; Tang, C.; Kotera, H. & Liu, L.
  • Journal Title: Stem Cell Reports Volume: 11 Issue: 1 Pages: 142-156
  • DOI: 10.1016/j.stemcr.2018.06.003
  • NAID: 120006488610
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dynamic Contact Guidance of Myoblasts by Feature Size and Reversible Switching of Substrate Topography: Orchestration of Cell Shape, Orientation, and Nematic Ordering of Actin Cytoskeletons. (2018)
  • Author(s): Linke, P.; Suzuki, R.; Yamamoto, A.; Nakahata, M.; Kengaku, M.; Fujiwara, T.; Ohzono, T.* & Tanaka, M.*
  • Journal Title: Langmuir Volume: special issue Issue: 23 Pages: 7538-7551
  • DOI: 10.1021/acs.langmuir.8b02972
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] HIV-1 Nef Disrupts CD4+ T Lymphocyte Polarity, Extravasation, and Homing to Lymph Nodes via Its Nef-Associated Kinase Complex Interface. (2018)
  • Author(s): Lamas-Murua, M.; Stolp, B.; Kaw, S.; Thoma, J.; Tsopoulidis, N.; Trautz, B.; Ambiel, I.; Reif, T.; Arora, S.; Imle, A.; Tibroni, N.; Wu. J.; Cui, G.; Stein, J. V.; Tanaka, M.; Lyck, R. & Fackler, O. T.
  • Journal Title: J. Immunol Volume: 201 Issue: 9 Pages: 2731-2743
  • DOI: 10.4049/jimmunol.1701420
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Lensless Tomographic Imaging of Near Surface Structures of Frozen Hydrated Malaria-Infected Human Erythrocytes by Coherent X-Ray Diffraction Microscopy (2017)
  • Author(s): Frank, Viktoria; Chushkin, Yuriy; Froehlich, Benjamin; Abuillan, Wasim; Rieger, Harden; Becker, Alexandra S.; Yamamoto, Akihisa; Rossetti, Fernanda F.; Kaufmann, Stefan、Lanzer, Michael; Zontone, Federico; Tanaka, Motomu
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 1-9
  • DOI: 10.1038/s41598-017-14586-4
  • NAID: 120006540180
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Supported membranes as a platform for dynamic phenotyping of primary human cells: Quantifying the effect of intrinsic and extrinsic factors (2019)
  • Author(s): M. Tanaka
  • Organizer: American Chemical Society Spring Meeting
  • Int'l Joint Research / Invited
• [Presentation] Supported Membranes: Platform for Dynamic Phenotyping of Diseases (2019)
  • Author(s): M. Tanaka
  • Organizer: Institute Colloquium, Institute Charles Sadron
  • Int'l Joint Research / Invited
• [Presentation] Human Corneal Endothelium as 2D Colloidal Assembly (2019)
  • Author(s): M. Tanaka ; A. Yamamoto
  • Organizer: Okinawa Colloid 2019
  • Int'l Joint Research / Invited
• [Presentation] Nano-to-Meso Confinement Regulates the Fate of Cells (2019)
  • Author(s): M. Tanaka
  • Organizer: Debugging Nanibio-Interfaces to Promote Clinical Translation
  • Int'l Joint Research / Invited
• [Presentation] Supported membranes as a platform for dynamic phenotyping of primary human cells: Quantifying the effect of intrinsic and extrinsic factors, (2019)
  • Author(s): M. Tanaka,
  • Organizer: American Society Meeting
  • Int'l Joint Research / Invited
• [Presentation] Coherent X-Ray Diffraction Imaging of Frozen Hydrated Human Erythrocytes Infected by Malaria Parasites (2018)
  • Author(s): M. Tanaka
  • Organizer: European X-Ray Diffraction Conference (EPDIC)
  • Int'l Joint Research / Invited
• [Presentation] Quantification of biomechanical properties of P.falciparum-infected hemoglobinopathic erythrocytes: Understanding the protective mechanism against severe forms of malaria (2017)
  • Author(s): Benjamin Froehlich
  • Organizer: System Biology of Human Disease
  • Int'l Joint Research
• [Presentation] In vitro models to investigate the interaction between lipids and mucin: a microinterferometric study (2017)
  • Author(s): Federico Amadei and Motomu Tanaka
  • Organizer: European Colloid and Interface Science Conference,
  • Int'l Joint Research
• [Book] Stem Cell Mobilization Methods and Protocols (2019)
  • Author(s): (Edited by) Gerd Klein, Patrick Wuchter
  • Total Pages: 250
  • Publisher: Humana Press
  • ISBN: 9781493995738
• [Patent(Industrial Property Rights)] 培地用高分子ゲル、培地、細胞の培養方法及びキット (2019)
  • Inventor(s): 原田明、高島義徳、中畑雅樹、田中求、M.Horning
  • Industrial Property Rights Holder: 原田明、高島義徳、中畑雅樹、田中求、M.Horning
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
  • Overseas
• [Patent(Industrial Property Rights)] 培地用高分子ゲル、培地、細胞の培養方法及びキット (2019)
  • Inventor(s): 原田明、高島義徳、中畑雅樹、田中求、M.Horning
  • Industrial Property Rights Holder: 原田明、高島義徳、中畑雅樹、田中求、M.Horning
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
  • Overseas
• [Patent(Industrial Property Rights)] 培地用高分子ゲル、培地、細胞の培養方法及びキット (2018)
  • Inventor(s): 原田明、高島義徳、中畑雅樹、田中求、M.Horning
  • Industrial Property Rights Holder: 原田明、高島義徳、中畑雅樹、田中求、M.Horning
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018