Advertisement

Influence of fabrication parameters in cellular microarrays for stem cell studies

  • Santiago A. Rodríguez-SeguíEmail author
  • Mateu Pla-Roca
  • Elisabeth Engel
  • Josep A. Planell
  • Elena Martínez
  • Josep SamitierEmail author
Article

Abstract

Lately there has been an increasing interest in the development of tools that enable the high throughput analysis of combinations of surface-immobilized signaling factors and which examine their effect on stem cell biology and differentiation. These surface-immobilized factors function as artificial microenvironments that can be ordered in a microarray format. These microarrays could be useful for applications such as the study of stem cell biology to get a deeper understanding of their differentiation process. Here, the evaluation of several key process parameters affecting the cellular microarray fabrication is reported in terms of its effects on the mesenchymal stem cell culture time on these microarrays. Substrate and protein solution requirements, passivation strategies and cell culture conditions are investigated. The results described in this article serve as a basis for the future development of cellular microarrays aiming to provide a deeper understanding of the stem cell differentiation process.

Keywords

PMMA Protein Spot Cell Seeding Microcontact Printing PMMA Substrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

S. A. Rodríguez-Seguí and E. Martínez acknowledge funding of the Spanish Ministry of Education through FPU and Ramón y Cajal Grants, respectively. M. Funes and Dr. C. A. Mills (Barcelona Science Park) are gratefully acknowledged for helping with the cell cultures and for comments with respect to the article. This paper and the work it concerns were generated in the context of the CellPROM project, funded by the European Community as Contract No. NMP4-CT-2004-500039 and it reflects only the authors’ views.

References

  1. 1.
    MacBeath G, Schreiber SL. Printing proteins as microarrays for high-throughput function determination. Science. 2000;289(5485):1760–3.PubMedADSGoogle Scholar
  2. 2.
    Flaim CJ, Chien S, Bhatia SN. An extracellular matrix microarray for probing cellular differentiation. Nat Methods. 2005;2(2):119–25.PubMedCrossRefGoogle Scholar
  3. 3.
    Kuschel C, Steuer H, Maurer AN, Kanzok B, Stoop R, Angres B. Cell adhesion profiling using extracellular matrix protein microarrays. Biotechniques. 2006;40(4):523–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Hook AL, Thissen H, Voelcker NH. Surface manipulation of biomolecules for cell microarray applications. Trends Biotechnol. 2006;24(10):471–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Falconnet D, Csucs G, Grandin HM, Textor M. Surface engineering approaches to micropattern surfaces for cell-based assays. Biomaterials. 2006;27(16):3044–63.PubMedCrossRefGoogle Scholar
  6. 6.
    Abhyankar VV, Beebe DJ. Spatiotemporal micropatterning of cells on arbitrary substrates. Anal Chem. 2007;79(11):4066–73.PubMedCrossRefGoogle Scholar
  7. 7.
    Chin VI, Taupin P, Sanga S, Scheel J, Gage FH, Bhatia SN. Microfabricated platform for studying stem cell fates. Biotechnol Bioeng. 2004;88(3):399–415.PubMedCrossRefGoogle Scholar
  8. 8.
    Thery M, Racine V, Pepin A, Piel M, Chen Y, Sibarita JB, et al. The extracellular matrix guides the orientation of the cell division axis. Nat Cell Biol. 2005;7(10):947–53.PubMedCrossRefGoogle Scholar
  9. 9.
    McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004;6(4):483–95.PubMedCrossRefGoogle Scholar
  10. 10.
    Lee JY, Shah SS, Zimmer CC, Liu GY, Revzin A. Use of photolithography to encode cell adhesive domains into protein microarrays. Langmuir. 2008;24(5):2232–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Derda R, Li LY, Orner BP, Lewis RL, Thomson JA, Kiessling LL. Defined substrates for human embryonic stem cell growth identified from surface arrays. Acs Chem Biol. 2007;2(5):347–55.PubMedCrossRefGoogle Scholar
  12. 12.
    Mei Y, Goldberg M, Anderson D. The development of high-throughput screening approaches for stem cell engineering. Curr Opin Chem Biol. 2007;11(4):388–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Underhill GH, Bhatia SN. High-throughput analysis of signals regulating stem cell fate and function. Curr Opin Chem Biol. 2007;11(4):357–66.PubMedCrossRefGoogle Scholar
  14. 14.
    Soen Y, Mori A, Palmer TD, Brown PO. Exploring the regulation of human neural precursor cell differentiation using arrays of signaling microenvironments. Mol Syst Biol. 2006;2:37.PubMedCrossRefGoogle Scholar
  15. 15.
    Peterbauer T, Heitz J, Olbrich M, Hering S. Simple and versatile methods for the fabrication of arrays of live mammalian cells. Lab Chip. 2006;6(7):857–63.PubMedCrossRefGoogle Scholar
  16. 16.
    Flaim CJ, Teng D, Chien S, Bhatia SN. Combinatorial signaling microenvironments for studying stem cell fate. Stem Cells Dev. 2008;17(1):29–39.PubMedCrossRefGoogle Scholar
  17. 17.
    Nakajima M, Ishimuro T, Kato K, Ko IK, Hirata I, Arima Y, et al. Combinatorial protein display for the cell-based screening of biomaterials that direct neural stem cell differentiation. Biomaterials. 2007;28(6):1048–60.PubMedCrossRefGoogle Scholar
  18. 18.
    Mills CA, Fernandez JG, Martinez E, Funes M, Engel E, Errachid A, et al. Directional alignment of MG63 cells on polymer surfaces containing point microstructures. Small. 2007;3(5):871–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Hyun J, Zhu YJ, Liebmann-Vinson A, Beebe TP, Chilkoti A. Microstamping on an activated polymer surface: patterning biotin and streptavidin onto common polymeric biomaterials. Langmuir. 2001;17(20):6358–67.CrossRefGoogle Scholar
  20. 20.
    Nelson CM, Raghavan S, Tan JL, Chen CS. Degradation of micropatterned surfaces by cell-dependent and -independent processes. Langmuir. 2003;19(5):1493–9.CrossRefGoogle Scholar
  21. 21.
    Lussi JW, Falconnet D, Hubbell JA, Textor M, Csucs G. Pattern stability under cell culture conditions—a comparative study of patterning methods based on PLL-g-PEG background passivation. Biomaterials. 2006;27(12):2534–41.PubMedCrossRefGoogle Scholar
  22. 22.
    Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science (New York, NY). 1999;284(5411):143–7.ADSGoogle Scholar
  23. 23.
    Gimble JM, Zvonic S, Floyd ZE, Kassem M, Nuttall ME. Playing with bone and fat. J Cell Biochem. 2006;98(2):251–66.PubMedCrossRefGoogle Scholar
  24. 24.
    Hughes FJ, Turner W, Belibasakis G, Martuscelli G. Effects of growth factors and cytokines on osteoblast differentiation. Periodontology. 2006;41:48–72.CrossRefGoogle Scholar
  25. 25.
    Muraglia A, Cancedda R, Quarto R. Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J Cell Sci. 2000;113(7):1161–6.PubMedGoogle Scholar
  26. 26.
    Tuli R, Tuli S, Nandi S, Wang ML, Alexander PG, Haleem-Smith H, et al. Characterization of multipotential mesenchymal progenitor cells derived from human trabecular bone. Stem Cells. 2003;21(6):681–93.PubMedCrossRefGoogle Scholar
  27. 27.
    Celil AB, Hollinger JO, Campbell PG. Osx transcriptional regulation is mediated by additional pathways to BMP2/Smad signaling. J Cell Biochem. 2005;95(3):518–28.PubMedCrossRefGoogle Scholar
  28. 28.
    Celil AB, Campbell PG. BMP-2 and insulin-like growth factor-I mediate Osterix (Osx) expression in human mesenchymal stem cells via the MAPK and protein kinase D signaling pathways. J Biol Chem. 2005;280(36):31353–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Gori F, Thomas T, Hicok KC, Spelsberg TC, Riggs BL. Differentiation of human marrow stromal precursor cells: bone morphogenetic protein-2 increases OSF2/CBFA1, enhances osteoblast commitment, and inhibits late adipocyte maturation. J Bone Miner Res. 1999;14(9):1522–35.PubMedCrossRefGoogle Scholar
  30. 30.
    Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126(4):677–89.PubMedCrossRefGoogle Scholar
  31. 31.
    Boland GM, Perkins G, Hall DJ, Tuan RS. Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem. 2004;93(6):1210–30.PubMedCrossRefGoogle Scholar
  32. 32.
    Miller ED, Fisher GW, Weiss LE, Walker LM, Campbell PG. Dose-dependent cell growth in response to concentration modulated patterns of FGF-2 printed on fibrin. Biomaterials. 2006;27(10):2213–21.PubMedCrossRefGoogle Scholar
  33. 33.
    Maniatopoulos C, Sodek J, Melcher AH. Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats. Cell Tissue Res. 1988;254(2):317–30.PubMedCrossRefGoogle Scholar
  34. 34.
    McCulloch CA, Strugurescu M, Hughes F, Melcher AH, Aubin JE. Osteogenic progenitor cells in rat bone marrow stromal populations exhibit self-renewal in culture. Blood. 1991;77(9):1906–11.PubMedGoogle Scholar
  35. 35.
    Dalby MJ, Gadegaard N, Tare R, Andar A, Riehle MO, Herzyk P, et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater. 2007;6(12):997–1003.PubMedCrossRefADSGoogle Scholar
  36. 36.
    Doyle A, Mather JP. Chapter 3. In: Doyle A, Griffiths JB, editors. Cell and tissue culture: laboratory procedures in biotechnology. New York: Wiley; 1998. p. 83–91.Google Scholar
  37. 37.
    Koblinski JE, Wu M, Demeler B, Jacob K, Kleinman HK. Matrix cell adhesion activation by non-adhesion proteins. J Cell Sci. 2005;118(Pt 13):2965–74.PubMedCrossRefGoogle Scholar
  38. 38.
    Bilgen B, Orsini E, Aaron RK, Ciombor DM. FBS suppresses TGF-beta1-induced chondrogenesis in synoviocyte pellet cultures while dexamethasone and dynamic stimuli are beneficial. J Tissue Eng Regen Med. 2008;1(6):436–42.CrossRefGoogle Scholar
  39. 39.
    Mackay AM, Beck SC, Murphy JM, Barry FP, Chichester CO, Pittenger MF. Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow. Tissue Eng. 1998;4(4):415–28.PubMedCrossRefGoogle Scholar
  40. 40.
    Barrett DG, Yousaf MN. Rapid patterning of cells and cell co-cultures on surfaces with spatial and temporal control through centrifugation. Angew Chem Int Ed Engl. 2007;46(39):7437–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Santiago A. Rodríguez-Seguí
    • 1
    • 2
    • 4
    Email author
  • Mateu Pla-Roca
    • 1
  • Elisabeth Engel
    • 1
    • 3
  • Josep A. Planell
    • 1
    • 3
  • Elena Martínez
    • 1
    • 4
  • Josep Samitier
    • 1
    • 2
    • 4
    Email author
  1. 1.Nanobioengineering Group and Bio/Non-bio Interactions for Regenerative Medicine GroupInstitute for Bioengineering of Catalonia (IBEC)BarcelonaSpain
  2. 2.Department of ElectronicsUniversity of BarcelonaBarcelonaSpain
  3. 3.Department of Materials Science and MetallurgyUniversitat Politècnica de CatalunyaBarcelonaSpain
  4. 4.Networking Research Center on BioengineeringBiomaterials and Nanomedicine (CIBER-BBN)BarcelonaSpain

Personalised recommendations