Biomechanical force-sensing and response mechanisms in vascular cells and its application to tissue engineering

2009 Fiscal Year Final Research Report

• Project/Area Number: 17076002
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: The University of Tokyo
• Principal Investigator: ANDO Joji The University of Tokyo, 医学部, 特任教授 (20159528)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Kimiko 東京大学, 大学院・医学系研究科, 講師 (00323618)
• Project Period (FY): 2005 – 2009
• Keywords: 血管 / 剪断応力 / 伸展張力 / ES細胞 / 内皮細胞 / 平滑筋細胞 / 再生医療

Research Abstract

Embryonic stem cells (ES cells) are attracting interests as a promising source of cells for use in regenerative medicine. The aim of the present study was to investigate whether biomechanical forces such as shear stress and cyclic strain affect ES cell differentiation. Fluid shear stress induced differentiation of cultured murine ES cell-derived VEGF receptor 2-positive (VEGFR2^+) cells into endothelial cells (ECs), whereas cyclic strain promoted the differentiation of the cells into smooth muscle cells (SMCs). Thus, it seems likely that biomechanical forces act as key regulators of early vascular development in the embryo. Moreover, biomechanical force may provide an invaluable tool to directly control ES cell differentiation in the field of tissue engineering.

Research Products

• [Journal Article] Vascular Mechanobiology: Endothelial Cell Responses to Fluid Shear Stress. (2009)
  • Author(s): J. Ando, K. Yamamoto
  • Journal Title: Circ. J. 73 Pages: 1983-1992
  • Peer Reviewed
• [Journal Article] Shear stress increases expression of the arterial endothelial markear ephrinB2 in murine ES cells via the VEGF-Notch signaling pathways. Arterioscler. (2009)
  • Author(s): T. Masumura, K. Yamamoto, N. Shimizu, S. Obi, J. Ando
  • Journal Title: Thromb. Vasc. Biol. 29 Pages: 2125-2131
  • Peer Reviewed
• [Journal Article] Fluid shear stress induces arterial differentiation of endothelial progenitor cells. (2009)
  • Author(s): S. Obi, K. Yamamoto, N. Shimizu, S. Kumagaya, T. Masumura, T. Sokabe, T. Asahara, J. Ando
  • Journal Title: J. Appl. Physiol 106 Pages: 203-211
  • Peer Reviewed
• [Journal Article] Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells by activating PDGF receptor (2008)
  • Author(s): N. Shimizu, K. Yamamoto, S. Obi, S. Kumagaya, T. Masumura, Y. Shimano, K. Naruse, J.K. Yamashita, T. Igarashi, J. Ando
  • Journal Title: J. Appl. Physiol. 104 Pages: 766-772
  • Peer Reviewed
• [Journal Article] Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch. (2008)
  • Author(s): M. Toda, K. Yamamoto, N Shimizu, S. Obi, S. Kumagaya, T. Igarashi, A. Kamiya, J. Ando
  • Journal Title: J. Biothechnol. 133 Pages: 239-244
• [Journal Article] Involvement of cell surface ATP synthase in flow-induced ATP release by vascular endothelial cells. (2007)
  • Author(s): K. Yamamoto, N. Shimizu, S. Obi, S. Kumagaya, Y. Taketani, A. Kamiya, J. Ando
  • Journal Title: Am. J. Physiol Heart Circ. Physiol 293 Pages: H1646-H1653
  • Peer Reviewed
• [Journal Article] Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. (2006)
  • Author(s): K. Yamamoto, T. Sokabe, T. Matsumoto, K. Yoshimura, M. Shibata, N. Ohura, T. Fukuda, K. Sekine, S. Kato, M. Isshiki, T. Fujita, M. Kobayashi, K. Kawamura, H. Masuda, A. Kamiya, J. Ando
  • Journal Title: Nat. Med. 12 Pages: 133-137
  • Peer Reviewed
• [Journal Article] Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading. (2005)
  • Author(s): H. Huang, Y. Nakayama, K. Qin, K. Yamamoto, J. Ando, J. Yamashita, H. Itoh, K. Kanda, H. Yaku, Y. Okamoto, Y. Nemoto
  • Journal Title: J. Artif. Organs 8 Pages: 110-118
  • Peer Reviewed
• [Journal Article] Fluid shear stress induces differentiation of Flk-1-positive embryonic stem cells into vascular endothelial cells in vitro. (2005)
  • Author(s): K. Yamamoto, T. Sokabe, T. Watabe, K. Miyzono, J. Yamashita, S. Obi, N. Ohura, A. Matsushita, A. Kamiya, J. Ando
  • Journal Title: Am. J. Physiol Heart Circ. Physiol 288 Pages: H1915-H1924
  • Peer Reviewed
• [Presentation] Shear-dependent mechanotransduction via endothelial ATP receptors and its physiological role in the vascular system. (2009)
  • Author(s): J. Ando
  • Organizer: The 36th International Congress of Physiological Sciences (IUPS2009) Kyoto
  • Place of Presentation: Japan
  • Year and Date: 2009-07-31
• [Presentation] Shear-stress-sensing and response mechanisms in vascular endothelial cells. (2009)
  • Author(s): J. Ando, K. Yamamoto
  • Organizer: The 3rd International Symposium for Interface Oral Health Science
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2009-01-15
• [Presentation] Shear stress mediated endothelial signaling and vascular homeostasis. (2008)
  • Author(s): J. Ando, K. Yamamoto
  • Organizer: The 13th International Conference on Biomedical Engineering
  • Place of Presentation: Singapore
  • Year and Date: 2008-12-05
• [Presentation] Cyclic strain induces mouse embryonic stem cell differentiation into vascular smooth muscle cells (2008)
  • Author(s): J. Ando, N. Shimizu, K. Yamamoto
  • Organizer: BMES Annual Fall Meeting
  • Place of Presentation: St. Louis, USA
  • Year and Date: 2008-10-02
• [Presentation] Induction of vascular cell differentiation by fluid-mechanical forces in embryonic stem cells. (2008)
  • Author(s): J. Ando, K. Yamamoto, N. Shimizu
  • Organizer: ISACB 11th Biennial Meeting
  • Place of Presentation: Bordeaux, France
  • Year and Date: 2008-09-19
• [Presentation] Shear-stress-sensing and response mechanisms in vascular endothelial cells. (2007)
  • Author(s): J. Ando
  • Organizer: The keynote lecture in NIH-funded Cellular Biotechnology Training Program Symposium
  • Place of Presentation: The University of Michigan, Ann Arbor
  • Year and Date: 2007-04-19
• [Presentation] The role of endothelial P2X4 receptors in flow-dependent control of vascular tone and remodeling. (2006)
  • Author(s): J. Ando, K. Yamamoto, T. Sokabe, A. Kamiya
  • Organizer: 5th World Congress of Biomechanics
  • Place of Presentation: Munich, Germany
  • Year and Date: 2006-08-03
• [Presentation] Shear stress induces differentiation of endothelial progenitor cells and embryonic stem stems into vascular endothelial cells (2005)
  • Author(s): J. Ando, K. Yamamoto
  • Organizer: Japan-Korean Joint Symposium on Vasculaar Biology
  • Place of Presentation: Doosan Resort, Chuncheon, Korea
  • Year and Date: 2005-08-11
• [Remarks]
  • URL: http://www.dokkyomed.ac.jp/dep-m/biomech/