Cell Exercise toward Elastic Cellular Tissue

2018 Fiscal Year Annual Research Report

• Project/Area Number: 15H05761
• Research Institution: Osaka University
• Principal Investigator: 金子 真 大阪大学, 工学研究科, 教授 (70224607)
• Co-Investigator(Kenkyū-buntansha): 東森 充 大阪大学, 工学研究科, 准教授 (30346522) ; 洞出 光洋 大阪大学, 工学研究科, 助教 (30583116) ; 横山 詩子 横浜市立大学, 医学部, 准教授 (70404994) ; 高山 俊男 大阪大学, 工学研究科, 准教授 (80376954)
• Project Period (FY): 2015-05-29 – 2019-03-31
• Keywords: Cell Exercise / 周期加圧 / 細胞培養 / 細胞シート / 動脈移植

Outline of Annual Research Achievements

(1)Cell Exercise方式と一定圧力方式とでいつ有意差が出るのか：マイクロチャンバを備えたマイクロ流路を２つ並列に配置した流路系をOn-Chip内に組み込み、両者に平滑筋細胞を播種した状態で、一方の流路は一定圧力、もう一方の流路はこれまでに得られた最適加圧条件を加え、顕微鏡で同時観察を行ったところ、細胞播種後わずか３０分で両者の間の形状に統計的有意差が見られた。
(2)弾力性の高い細胞シートができる条件：平滑筋細胞の選択肢としてはヒト臍帯動脈から採取した平滑筋細胞を用いて作製した細胞シートで引っ張り試験を行った結果、ヒトの動脈に匹敵する最大破断応力が得られ、ヒトの動脈移植の可能性も視野に入ってきた。また周波数0。002Hz(周期８分)に固定して、最大圧力を180kPaからさらに上げていくと、引っ張り弾力性がさらに増加していく傾向が確認できた。
(3)弾力性の高い細胞シートができたときに現れるバイオマーカ：弾力性の高い細胞シートが得られた場合、バイオ的視点で細胞シート内部でどんな遺伝子やたんぱく質が発現しているかを調べることは興味深い。この関係が明らかになれば、バイオマーカを調べるだけで、引っ張り試験をしなくても弾力性の高い細胞シートが出来ていることがわかるようになるからである。“Cell Exercise”後に弾力性の高い細胞シートに特別なタンパク質が現れることがわかった。
(4)滑筋細胞以外の細胞でCell Exerciseを行った場合：培養心筋細胞に対して、1分毎に100 kPaと300 kPaで交互に8時間圧負荷をかけた場合、圧負荷によるBNP遺伝子の発現上昇には、α1受容体とFGF受容体が関与することが明らかになった。このように心筋細胞に対してもCell Exerciseにより顕著な違いが見られた点は特筆に値する。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] Pohang Univ. of Sci. and Tech.(韓国)
  • Country Name: KOREA (REP. OF KOREA)
  • Counterpart Institution: Pohang Univ. of Sci. and Tech.
• [Int'l Joint Research] Heidelberg University(ドイツ)
  • Country Name: GERMANY
  • Counterpart Institution: Heidelberg University
• [Int'l Joint Research] National Chiao Tung University, Taiwan(その他の国・地域)
  • Country Name: その他の国・地域
  • Counterpart Institution: National Chiao Tung University, Taiwan
• [Journal Article] Usefulness of Exchanged Protein Directly Activated by cAMP (Epac)1-Inhibiting Therapy for Prevention of Atrial and Ventricular Arrhythmias in Mice (2019)
  • Author(s): Prajapati R, Fujita T, Suita K, Nakamura T, Cai W, Hidaka Y, Umemura M, Yokoyama U, Knollmann BC, Okumura S, and Ishikawa Y
  • Journal Title: Circ J Volume: 83 Pages: 295-303
  • DOI: 10.1253/circj.CJ-18-0743
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Antenatal Administration of Betamethasone Contributes to Intimal Thickening of the Rat Ductus Arteriosus (2019)
  • Author(s): Kemmotsu T, Yokoyama U, Saito J, Ito S, Uozumi A, Nishimaki S, Iwasaki S, Seki K, Ito S, and Ishikawa Y
  • Journal Title: Circ J Volume: 83 Pages: 654-661
  • DOI: 10.1253/circj.CJ-18-1033
  • Peer Reviewed / Open Access
• [Journal Article] Epac1 deficiency inhibits basic fibroblast growth factor-mediated vascular smooth muscle cell migration (2019)
  • Author(s): Kato Y, Yokoyama U, Fujita T, Umemura M, Kubota T, and Ishikawa Y
  • Journal Title: J Physiol Sci Volume: 69 Pages: 175-184
  • DOI: 10.1007/s12576-018-0631-7
  • Peer Reviewed / Open Access
• [Journal Article] Constrained Adherable Area of Nanotopographic Surfaces Promotes Cell Migration through the Regulation of Focal Adhesion via Focal Adhesion Kinase/Rac1 Activation (2018)
  • Author(s): Lim Jiwon、Choi Andrew、Kim Hyung Woo、Yoon Hyungjun、Park Sang Min、Tsai Chia-Hung Dylan、Kaneko Makoto、Kim Dong Sung
  • Journal Title: ACS Applied Materials & Interfaces Volume: 10 Pages: 14331～14341
  • DOI: 10.1021/acsami.7b18954
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] LED-CT Scan for pH Distribution on a Cross-Section of Cell Culture Medium (2018)
  • Author(s): Higashino Nobuya, Takayama Toshio, Ito Hiroaki, Horade Mitsuhiro, Yamaguchi Yasutaka, Dylan Tsai Chia-Hung, Kaneko Makoto
  • Journal Title: Sensors Volume: 18 Pages: 191～191
  • DOI: 10.3390/s18010191
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Simultaneous hyperthermia-chemotherapy effect by arterial injection of Fe(Salen) for femur tumor (2018)
  • Author(s): Umemura Masanari, Islam Md. Rafikul, Fukumura Hidenobu, Sato Itaru, Kawabata Yusuke, Matsuo Kousuke, Nakakaji Rina, Nagasako Akane, Ohtake Makoto, Takayuki Fujita, Yokoyama Utako, Nakayama Tomohiro, Eguchi Haruki, Ishikawa Yoshihiro
  • Journal Title: Cancer Science Volume: 110 Pages: 356～365
  • DOI: 10.1111/cas.13851
  • Peer Reviewed / Open Access
• [Journal Article] Proteomic analysis of aortic smooth muscle cell secretions reveals an association of myosin heavy chain 11 with abdominal aortic aneurysm (2018)
  • Author(s): Yokoyama U, Arakawa N, Ishiwata R, Yasuda S, Minami T, Goda M, Uchida K, Suzuki S, Matsumoto M, Koizumi N, Taguri M, Hirano H, Yoshimura K, Ogino H, Masuda M, and Ishikawa Y
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 315 Pages: H1012-H1018
  • DOI: 10.1152/ajpheart.00329.2018
  • Peer Reviewed / Open Access
• [Journal Article] Hydrostatic pressure suppresses fibrotic changes via Akt/GSK-3 signaling in human cardiac fibroblasts (2018)
  • Author(s): Tanaka R, Umemura M, Narikawa M, Fujita T, Yokoyama U, Ishigami T, Kimura K, Tamura K, and Ishikawa Y
  • Journal Title: Physiol Rep Volume: 6 Pages: e13687
  • DOI: 10.14814/phy2.13687
  • Peer Reviewed / Open Access
• [Journal Article] Vidarabine, an anti-herpesvirus agent, prevents catecholamine-induced arrhythmias without adverse effect on heart function in mice (2018)
  • Author(s): Suita K, Fujita T, Cai W, Hidaka Y, Jin H, Prajapati R, Umemura M, Yokoyama U, Sato M, Knollmann BC, Okumura S, and Ishikawa Y
  • Journal Title: Pflugers Arch Volume: 470 Pages: 923-935
  • DOI: 10.1007/s00424-018-2121-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acute Hyperthermia Inhibits TGF-beta1-induced Cardiac Fibroblast Activation via Suppression of Akt Signaling (2018)
  • Author(s): Narikawa M, Umemura M, Tanaka R, Fujita T, Yokoyama U, Ishigami T, Kimura K, Tamura K, and Ishikawa Y
  • Journal Title: Sci Rep Volume: 8 Pages: 6277
  • DOI: 10.1038/s41598-018-24749-6
  • Peer Reviewed / Open Access
• [Journal Article] Fabrication of engineered tubular tissue for small blood vessels via three-dimensional cellular assembly and organization ex vivo (2018)
  • Author(s): Masuda T, Ukiki M, Yamagishi Y, Matsusaki M, Akashi M, Yokoyama U, and Arai F
  • Journal Title: J Biotechnol Volume: 20 Pages: 46-53
  • DOI: 10.1016/j.jbiotec.2018.04.003
  • Peer Reviewed / Open Access
• [Journal Article] A selective antagonist of prostaglandin E receptor subtype 4 attenuates abdominal aortic aneurysm (2018)
  • Author(s): Mamun A, Yokoyama U, Saito J, Ito S, Hiromi T, Umemura M, Fujita T, Yasuda S, Minami T, Goda M, Uchida K, Suzuki S, Masuda M, and Ishikawa Y
  • Journal Title: Physiol Rep Volume: 6 Pages: e13878
  • DOI: 10.14814/phy2.13878
  • Peer Reviewed / Open Access
• [Journal Article] Alternating magnetic field enhances cytotoxicity of Compound C (2018)
  • Author(s): Akimoto T, Umemura M, Nagasako A, Ohtake M, Fujita T, Yokoyama U, Eguchi H, Yamamoto T, and Ishikawa Y
  • Journal Title: Cancer Sci Volume: 109 Pages: 3483-3493
  • DOI: 10.1111/cas.13781
  • Peer Reviewed / Open Access
• [Presentation] Gaseous components of cigarette smoke upregulate prostaglandin E2 receptor EP4 in aortic aneurysm (2019)
  • Author(s): Hiromi T, Yokoyama U, Takeuchi I, and Ishikawa Y
  • Organizer: The 9th Federation of the Asian and Oceanian Physiological Societies Congress
  • Int'l Joint Research / Invited
• [Presentation] How "Human arterial graft" should be fabricated? (2018)
  • Author(s): Yokoyama U
  • Organizer: CBS 2018- IEEE International Conference on Cyborg and Bionic Systems
  • Int'l Joint Research / Invited
• [Presentation] Mechanoresponse to periodic hydrostatic pressure enables fabrication of human arterial graft (2018)
  • Author(s): Saito J, Yokoyama U, Takayama T, Horade M, Ito H, Sugo Y, Kurasawa K, Ogawa M, Miyagi E, Kaneko M, and Ishikawa Y
  • Organizer: American Society for Matrix Biology Biennial Meeting 2018
  • Int'l Joint Research
• [Presentation] Prostaglandin E2 promotes vascular remodeling of the ductus arteriosus (2018)
  • Author(s): Minamisawa S, Akaike T, and Yokoyama U
  • Organizer: The 25th Euro Congress on Pediatric Heart Disease and Health
  • Int'l Joint Research
• [Presentation] Tissue-type plasminogen activator promotes intimal thickening formation of the ductus arteriosus (2018)
  • Author(s): Saito J, Yokoyama U, Nicho N, Zheng YW, Ito S, Ito S, Taniguchi H, Asou T, Masuda M, and Ishikawa Y
  • Organizer: Weinstein 2018 Cardiovascular Development and Regeneration Conference
  • Int'l Joint Research
• [Presentation] Antenatal administration of betamethasone promotes closure of the preterm ductus arteriosus via intimal thickening formation (2018)
  • Author(s): Kemmotsu T, Yokoyama U, Azuma S, Saito J, Ito S, Uozumi A, Nishimaki S, Iwasaki S, Seki K, Ito S, and Ishikawa Y
  • Organizer: Weinstein 2018 Cardiovascular Development and Regeneration Conference
  • Int'l Joint Research
• [Presentation] Prostaglandin E-EP4 signaling-mediated fibulin-1 integrates extracellular matrices to promote smooth muscle cell migration of the ductus arteriosus (2018)
  • Author(s): Ito S, Yokoyama U, Saito JZ, Y.W., Masuda M, Asou T, and Ishikawa Y
  • Organizer: Weinstein 2018 Cardiovascular Development and Regeneration Conference
  • Int'l Joint Research
• [Funded Workshop] 2018 Int. Workshop on Bio/Medical/Cognitive Science--Current and Future Direction-- (2018)