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Primary and Stem Cell Microarrays: Application as Miniaturized Biotesting Systems

  • Rebecca Jonczyk
  • Thomas Scheper
  • Frank Stahl
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1771)

Abstract

The deposition of living cells on microarray surfaces can be used to create physiologically relevant architecture in vitro. Such living cell microarrays enable the reconstruction of biological processes outside the body in a miniaturized format and have many advantages over traditional cell culture. The present protocol offers an option for the preparation and analysis of living primary and stem cell-based microarrays utilizing the standard microarray equipment (contact-free piezoelectric nanoprinter, microarray scanner), as well as microscopy. To produce living cell microarrays, we applied two kinds of mesenchymal stem cells (MSCs) isolated from umbilical cord and adipose tissue, as well as human umbilical vein endothelial cells (HUVECs) as model cells. We used live imaging microscopy for the online monitoring of cell spots in total size, staining of viable cells with Calcein acetoxymethyl ester (Calcein-AM) and treatment of MSCs with differentiation media to analyze the proliferation, viability, and differentiation potential of printed cells. This way, the general applicability of the established living cell-based microarray production was demonstrated.

Key words

Microarray technology Piezoelectric nanoprinting Living cell microarrays Primary human cells Mesenchymal stem cells Endothelial cells Online monitoring microscopy 

Notes

Acknowledgment

This work was supported by the BIOFABRICATION FOR NIFE Initiative, which is financially supported by the Lower Saxony ministry of Science and Culture and the VolkswagenStiftung. NIFE is the Lower Saxony Center for Biomedical Engineering, Implant Research and Development in Hannover, a joint translational research centre of the Hannover Medical School, the Leibniz Universität Hannover, the University of Veterinary Medicine Hannover, and the Laser Center Hannover.

References

  1. 1.
    Papp K, Szittner Z, Prechl J (2012) Life on a microarray: assessing live cell functions in a microarray format. Cell Mol Life Sci 69(16):2717–2725.  https://doi.org/10.1007/s00018-012-0947-zCrossRefGoogle Scholar
  2. 2.
    Cagnin S, Cimetta E, Guiducci C, Martini P, Lanfranchi G (2012) Overview of micro- and nano-technology tools for stem cell applications: micropatterned and microelectronic devices. Sensors 12(11):15947CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Xu T, Olson J, Zhao W, Atala A, Zhu J-M, Yoo JJ (2008) Characterization of cell constructs generated with inkjet printing technology using in vivo magnetic resonance imaging. J Manuf Sci Eng 130(2):021013–021013.  https://doi.org/10.1115/1.2902857CrossRefGoogle Scholar
  4. 4.
    Ziauddin J, Sabatini DM (2001) Microarrays of cells expressing defined cDNAs. Nature 411(6833):107–110.  https://doi.org/10.1038/35075114CrossRefGoogle Scholar
  5. 5.
    Yarmush ML, King KR (2009) Living-cell microarrays. Annu Rev Biomed Eng 11:235–257.  https://doi.org/10.1146/annurev.bioeng.10.061807.160502CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Angres B (2005) Cell microarrays. Expert Rev Mol Diagn 5(5):769–779.  https://doi.org/10.1586/14737159.5.5.769CrossRefGoogle Scholar
  7. 7.
    Jonczyk R, Kurth T, Lavrentieva A, Walter J-G, Scheper T, Stahl F (2016) Living cell microarrays: an overview of concepts. Microarrays 5(2):11CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Date A, Pasini P, Daunert S (2010) Fluorescent and bioluminescent cell-based sensors: strategies for their preservation. Adv Biochem Eng Biotechnol 117:57–75.  https://doi.org/10.1007/10_2009_22CrossRefPubMedGoogle Scholar
  9. 9.
    Hart T, Zhao A, Garg A, Bolusani S, Marcotte EM (2009) Human cell chips: adapting DNA microarray spotting technology to cell-based imaging assays. PLoS One 4(10):e7088.  https://doi.org/10.1371/journal.pone.0007088CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Rasi Ghaemi S, Harding F, Delalat B, Vasani R, Voelcker NH (2013) Surface engineering for long-term culturing of mesenchymal stem cell microarrays. Biomacromolecules 14(8):2675–2683.  https://doi.org/10.1021/bm400531nCrossRefPubMedGoogle Scholar
  11. 11.
    Suri S, Singh A, Nguyen AH, Bratt-Leal AM, McDevitt TC, Lu H (2013) Microfluidic-based patterning of embryonic stem cells for in vitro development studies. Lab Chip 13(23):4617–4624.  https://doi.org/10.1039/C3LC50663KCrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Saunders RE, Gough JE, Derby B (2008) Delivery of human fibroblast cells by piezoelectric drop-on-demand inkjet printing. Biomaterials 29(2):193–203.  https://doi.org/10.1016/j.biomaterials.2007.09.032CrossRefPubMedGoogle Scholar
  13. 13.
    Yusof A, Keegan H, Spillane CD, Sheils OM, Martin CM, O’Leary JJ, Zengerle R, Koltay P (2011) Inkjet-like printing of single-cells. Lab Chip 11(14):2447–2454.  https://doi.org/10.1039/c1lc20176jCrossRefPubMedGoogle Scholar
  14. 14.
    Xu T, Jin J, Gregory C, Hickman JJ, Boland T (2005) Inkjet printing of viable mammalian cells. Biomaterials 26(1):93–99.  https://doi.org/10.1016/j.biomaterials.2004.04.011CrossRefPubMedGoogle Scholar
  15. 15.
    Jonczyk R, Timur S, Scheper T, Stahl F (2016) Development of living cell microarrays using non-contact micropipette printing. J Biotechnol 217:109–111CrossRefPubMedGoogle Scholar
  16. 16.
    Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317.  https://doi.org/10.1080/14653240600855905CrossRefPubMedGoogle Scholar
  17. 17.
    Moretti P, Hatlapatka T, Marten D, Lavrentieva A, Majore I, Hass R, Kasper C (2010) Mesenchymal stromal cells derived from human umbilical cord tissues: primitive cells with potential for clinical and tissue engineering applications. Adv Biochem Eng Biotechnol 123:29–54.  https://doi.org/10.1007/10_2009_15CrossRefPubMedGoogle Scholar
  18. 18.
    Kuhbier JW, Weyand B, Radtke C, Vogt PM, Kasper C, Reimers K (2010) Isolation, characterization, differentiation, and application of adipose-derived stem cells. Adv Biochem Eng Biotechnol 123:55–105.  https://doi.org/10.1007/10_2009_24CrossRefPubMedGoogle Scholar
  19. 19.
    von der Haar M, Heuer C, Pahler M, von der Haar K, Lindner P, Scheper T, Stahl F (2016) Optimization of cyanine dye stability and analysis of FRET interaction on DNA microarrays. Biology 5(4).  https://doi.org/10.3390/biology5040047
  20. 20.
    Turinetto V, Vitale E, Giachino C (2016) Senescence in human mesenchymal stem cells: functional changes and implications in stem cell-based therapy. Int J Mol Sci 17(7):1164CrossRefPubMedCentralGoogle Scholar
  21. 21.
    Bala K, Ambwani K, Gohil NK (2011) Effect of different mitogens and serum concentration on HUVEC morphology and characteristics: Implication on use of higher passage cells. Tissue Cell 43(4):216–222.  https://doi.org/10.1016/j.tice.2011.03.004CrossRefPubMedGoogle Scholar
  22. 22.
    Siow RCM (2012) Culture of human endothelial cells from umbilical veins. In: Mitry RR, Hughes RD (eds) Human cell culture protocols. Humana Press, Totowa, NJ, pp 265–274.  https://doi.org/10.1007/978-1-61779-367-7_18CrossRefGoogle Scholar
  23. 23.
    Ferris CJ, Gilmore KJ, Beirne S, McCallum D, Wallace GG, in het Panhuis M (2013) Bio-ink for on-demand printing of living cells. Biomater Sci 1(2):224–230.  https://doi.org/10.1039/C2BM00114DCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Technical ChemistryGottfried Wilhelm Leibniz Universität HannoverHannoverGermany

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