Skip to main content

Advertisement

SpringerLink
Log in

Characterisation of human induced pluripotent stem cell-derived endothelial cells under shear stress using an easy-to-use microfluidic cell culture system

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

Induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) can contribute to elucidating the pathogenesis of heart and vascular diseases and developing their treatments. Their precise characteristics in fluid flow however remain unclear. Therefore, the aim of the present study is to characterise these features. We cultured three types of ECs in a microfluidic culture system: commercially available human iPS-ECs, human umbilical vein endothelial cells (HUVECs) and human umbilical artery endothelial cells (HUAECs). We then examined the mRNA expression levels of endothelial marker gene cluster of differentiation 31 (CD31), fit-related receptor tyrosine kinase (Flk-1), and the smooth muscle marker gene smooth muscle alpha-actin, and investigated changes in plasminogen activator inhibitor-1 (PAI-1) secretion and intracellular F-actin arrangement following heat stress. We also compared expressions of the arterial and venous marker genes ephrinB2 and EphB4, and the endothelial gap junction genes connexin (Cx) 37, 40, and 43 under fluidic shear stress to determine their arterial or venous characteristics. We found that iPS-ECs had similar endothelial marker gene expressions and exhibited similar increases in PAI-1 secretion under heat stress as HUVECs and HUAECs. In addition, F-actin arrangement in iPSC-ECs also responded to heat stress, as previously reported. However, they had different expression patterns of arterial and venous marker genes and Cx genes under different fluidic shear stress levels, showing that iPSC-ECs exhibit different characteristics from arterial and venous ECs. This microfluidic culture system equipped with variable shear stress control will provide an easy-to-use assay tool to examine characteristics of iPS-ECs generated by different protocols in various laboratories and contribute to basic and applied biomedical researches on iPS-ECs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • A.C. Brisset, B.E. Isakson, B.R. Kwak, Antioxid. Redox Signal. 11, 267 (2009)

    Article  Google Scholar 

  • Q. Chen, H. Zhang, Y. Liu, S. Adams, H. Eilken, M. Stehling, M. Corada, E. Dejana, B. Zhou, R.H. Adams, Nat. Commun. 7, 12422 (2016)

    Article  Google Scholar 

  • L.J. Chen, S. Ito, H. Kai, K. Nagamine, N. Nagai, M. Nishizawa, T. Abe, H. Kaji, Sci. Rep. 7, 3538 (2017)

    Article  Google Scholar 

  • J.E. Deanfield, J.P. Halcox, T.J. Rabelink, Circulation 115(10), 1285 (2007)

    Google Scholar 

  • A. Eichmann, C. Corbel, V. Nataf, P. Vaigot, C. Bréant, N.M. Le Douarin, Proc. Natl. Acad. Sci. U. S. A. 94, 5141 (1997)

    Article  Google Scholar 

  • O. Hadadeh, E. Barruet, F. Peiretti, M. Verdier, D. Bernot, Y. Hadjal, C.E. Yazidi, A. Robaglia-Schlupp, A.M. De Paula, D. Nègre, M. Iacovino, M. Kyba, M.C. Alessi, B. Binétruy, PLoS One 7, e49065 (2012)

    Article  Google Scholar 

  • S. Hamauchi, U. Shichinohe, H. Uchino, S. Yamaguchi, N. Nakayama, K. Kazumata, T. Osanai, T. Abumiya, K. Houkin, T. Era, PLoS One 11, e0163561 (2016)

    Article  Google Scholar 

  • M.A. Hervé, G. Meduri, F.G. Petit, T.S. Domet, G. Lazennec, S. Mourah, M. Perrot-Applanat, J. Endocrinol. 188, 91 (2006)

    Article  Google Scholar 

  • T. Ikuno, H. Masumoto, K. Yamamizu, M. Yoshioka, K. Minakata, T. Ikeda, R. Sakata, J.K. Yamashita, PLoS One 12, e0173271 (2017)

    Article  Google Scholar 

  • T. Inai, M.R. Mancuso, D.M. McDonald, J. Kobayashi, K. Nakamura, Y. Shibata, Histochem. Cell Biol. 122, 477 (2004)

    Article  Google Scholar 

  • T.L. Johnson, R.M. Nerem, Endothelium 14, 215 (2007)

    Article  Google Scholar 

  • A. Kamiya, R. Bukhari, T. Togawa, Bull. Math. Biol. 46, 127 (1984)

    Article  Google Scholar 

  • N.M. Kane, Q. Xiao, A.H. Baker, Z. Luo, Q. Xu, C. Emanueli, Pharmacol. Ther. 129, 29 (2011)

    Article  Google Scholar 

  • S. Kashiwagi, Y. Izumi, T. Gohongi, Z.N. Demou, L. Xu, P.L. Huang, D.G. Buerk, L.L. Munn, R.K. Jain, D. Fukumura, J. Clin. Invest. 115, 1816 (2005)

    Article  Google Scholar 

  • S. Kathiresan, D. Srivastava, Cell 148, 1242 (2012)

    Article  Google Scholar 

  • M.E. Katt, Z.S. Xu, S. Gerecht, P.C. Searson, PLoS One 11, e0152105 (2016)

    Article  Google Scholar 

  • N.J. Leeper, A.L. Hunter, J.P. Cooke, Circulation 122, 517 (2010)

    Article  Google Scholar 

  • E.S. Lippmann, A. Al-Ahmad, S.M. Azarin, S.P. Palecek, E.V. Shusta, Sci Rep 4, 4160 (2014)

    Article  Google Scholar 

  • H. Minami, K. Tashiro, A. Okada, N. Hirata, T. Yamaguchi, K. Takayama, H. Mizuguchi, K. Kawabata, PLoS One 10, e0128890 (2015)

    Article  Google Scholar 

  • T.G. Papaioannou, C. Stefanadis, Hell. J. Cardiol. 46, 9 (2005)

    Google Scholar 

  • A. Pfenniger, C. Wong, E. Sutter, S. Cuhlmann, S. Dunoyer-Geindre, F. Mach, A.J. Horrevoets, P.C. Evans, R. Krams, B.R. Kwak, J. Mol. Cell. Cardiol. 53, 299 (2012)

    Article  Google Scholar 

  • A.J. Rufaihah, N.F. Huang, S. Jame, J.C. Lee, H.N. Nguyen, B. Byers, A. De, J. Okogbaa, M. Rollins, R. Reijo-Pera, S.S. Gambhir, J.P. Cooke, Arterioscler. Thromb. Vasc. Biol. 31, e72–e79 (2011)

    Article  Google Scholar 

  • K. Sato, M. Nakajima, S. Tokuda, A. Ogawa, Anal. Sci. 32, 1217 (2016)

    Article  Google Scholar 

  • F. Shalaby, J. Rosant, T.P. Yamaguchi, M. Gertsenstein, X.F. Wu, M.L. Breitman, A.C. Schuh, Nature 376, 62 (1995)

    Article  Google Scholar 

  • H. Stockinger, S.J. Gadd, R. Eher, O. Majdic, W. Schreiber, W. Kasinrerk, B. Strass, E. Schnabl, W. Knapp, J. Immunol. 145, 3889 (1990)

    Google Scholar 

  • H. Suzuki, R. Shibata, T. Kito, M. Ishii, P. Li, T. Yoshikai, N. Nishio, S. Ito, Y. Numaguchi, J.K. Yamashita, T. Murohara, K. Isobe, BMC Cell Biol. 11, 72 (2010). https://doi.org/10.1186/1471-2121-11-72

    Article  Google Scholar 

  • K. Takahashi, K. Tanabe, M. Ohnuki, M. Narita, T. Ichisaka, K. Tomoda, S. Yamanaka, Cell 131(5), 861 (2007)

    Article  Google Scholar 

  • K.S. Tan, K. Tamura, M.I. Lai, A. Veerakumarasivam, Y. Nakanishi, M. Ogawa, D. Sugiyama, Stem Cell Rev. 9, 586 (2013)

    Article  Google Scholar 

  • H. Tazawa, K. Sato, A. Tsutiya, M. Tokeshi, R. Ohtani-Kaneko, Thromb. Res. 136, 328 (2015)

    Article  Google Scholar 

  • H. Tazawa, S. Sunaoshi, M. Tokeshi, T. Kitamori, R. Ohtani-Kaneko, Anal. Sci. 32, 349 (2016)

    Article  Google Scholar 

  • J.A. van Mourik, O.C. Leeksma, J.H. Reinders, P.G. de Groot, J. Zandbergen-Spaargaren, J. Biol. Chem. 260, 11300 (1985)

    Google Scholar 

  • K.S. Volz, E. Miljan, A. Khoo, J.P. Cooke, Vasc Pharmacol 56, –288 (2012)

  • B.J. Vorderwülbecke, J. Maroski, K. Fiedorowicz, L. Da Silva-Azevedo, A. Marki, A.R. Pries, A. Zakrzewicz, Am. J. Physiol. Heart Circ. Physiol. 302, H143 (2012)

    Article  Google Scholar 

  • H.U. Wang, Z.F. Chen, D.J. Anderson, Cell 93(5), 741 (1998)

    Article  Google Scholar 

  • T.P. Yamaguchi, D.J. Dumont, R.A. Conlon, M.L. Breitman, J. Rossant, Development 118, 489 (1993)

    Google Scholar 

  • J. Yamashita, H. Itoh, M. Hirashima, M. Ogawa, S. Nishikawa, T. Yurugi, M. Naito, K. Nakao, S. Nishikawa, Nature 408, 92 (2000)

    Article  Google Scholar 

  • X. Zhang, P. Jones, S.J. Haswell, Chem. Eng. J. 135S, S82 (2008)

    Article  Google Scholar 

Download references

Acknowledgements

This study was partially supported by Research Center for Biomedical Engineering in Toyo University. This study was also partially supported by Life Innovation Research Center in Toyo University.

Author information

Authors and Affiliations

  1. Department of Life Sciences, Toyo University, 1-1-1 Itakura, Oura, Gunma, 374-0193, Japan

    Rsituko Ohtani-Kaneko, Kenjiro Sato, Yuka Nakagawa & Kazutoshi Hashizume

  2. Department of Biochemistry, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, 216-8511, Japan

    Atsuhiro Tsutiya

  3. Institute of Microchemical Technology Co., Ltd., 713A West KSP, 3-2-1 Sakado, Takatsu, Kawasaki, 213-0012, Japan

    Hidekatsu Tazawa

Authors
  1. Rsituko Ohtani-Kaneko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenjiro Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Atsuhiro Tsutiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuka Nakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazutoshi Hashizume
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hidekatsu Tazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rsituko Ohtani-Kaneko.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ohtani-Kaneko, R., Sato, K., Tsutiya, A. et al. Characterisation of human induced pluripotent stem cell-derived endothelial cells under shear stress using an easy-to-use microfluidic cell culture system. Biomed Microdevices 19, 91 (2017). https://doi.org/10.1007/s10544-017-0229-5

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s10544-017-0229-5

Keywords

Search

Navigation