Biomedical Microdevices

, Volume 8, Issue 1, pp 65–71 | Cite as

Elucidating in vitro cell-cell interaction using a microfluidic coculture system

Article

Abstract

This work presents a novel microfluidic coculture system that improves the accuracy of evaluating the interaction between cocultured cell types. A microfluidic coculture chip, fabricated by CO2 laser direct-writing on polymethyl methacrylate (PMMA), was designed to separate two cell types using a microchannel, while permitting transfer of cellular media. The system has two up-stream wells and five down-stream wells. As an example, released inflammatory cytokines (e.g., interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), activated in up-stream macrophages, flow through a microfluidic mixing system, generating linear concentration gradients in down-stream wells and inducing down-stream osteoblasts to release prostaglandin E2 (PGE2), a well-known bone resorption marker. Osteoblast viability was assessed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. This novel coculture system can be applied to evaluate cell-cell interaction while physically separating interacting cells.

Keywords

Microfluidic Coculture Cell-cell interaction 

References

  1. M.A. Attawia and J.J. Nicholsonand C.T. Laurencin, Clin Orthop 230–236 (1999).Google Scholar
  2. J.Y. Cheng, C.W. Wei and K.H. Hsuand T.H. Young, Sensors and Actuators B: Chemical 99, 186–196 (2004).Google Scholar
  3. H. Gelb, H.R. Schumacher, J. Cuckler and P. Ducheyneand D.G. Baker, J Orthop Res 12, 83–92 (1994).Google Scholar
  4. T.T. Glant, J.J. Jacobs, G. Molnar, A.S. Shanbhag and M. Valyonand J.O. Galante, J Bone Miner Res 8, 1071–1079 (1993).Google Scholar
  5. D. Granchi, G. Ciapetti, I. Amato, S. Pagani and E. CenniL. Savarino, S. Avnet, J.L. Peris, A. Pellacani, N. Baldini, and A. Giunti, Biomaterials 25, 4037–4045 (2004).CrossRefGoogle Scholar
  6. T.R. Green, J. Fisher, J.B. Matthews and M.H. Stoneand E. Ingham, J Biomed Mater Res 53, 490–497 (2000).CrossRefGoogle Scholar
  7. S.M. Horowitz, B.P. Rapuano and J.M. Laneand A.H. Burstein, Calcif Tissue Int 54, 320–324 (1994).CrossRefGoogle Scholar
  8. S.L. Hsuan, M.S. Kannan, S. Jeyaseelan, Y.S. Prakash and G.C. Sieckand S.K. Maheswaran, Infect Immun 66, 2836–2844 (1998).Google Scholar
  9. E. Ingham, T.R. Green, M.H. Stone, R. Kowalski and N. Watkinsand J. Fisher, Biomaterials 21, 1005–1013 (2000).CrossRefGoogle Scholar
  10. Y. Jiang, C.K. Mehta and T.Y. Hsuand F.F. Alsulaimani, Infect Immun 70, 3143–3148 (2002).Google Scholar
  11. F.Y. Jin, C. Nathan and D. Radziochand A. Ding, Cell 88, 417–426 (1997).CrossRefGoogle Scholar
  12. T. Kirikae, F.U. Schade, F. Kirikae and E.T. Rietscheland D.C. Morrison, J Immunol 151, 2742–2752 (1993).Google Scholar
  13. P. Lavigne, Q. Shi, F.C. Jolicoeur, J.P. Pelletier, J. Martel-Pelletier and J.C. Fernandes, Osteoarthritis Cartilage 10, 898–904 (2002).CrossRefGoogle Scholar
  14. P. Lavigne, Q. Shi, D. Lajeunesse and F. Dehnadeand J.C. Fernandes, Bone 34, 478–486 (2004).CrossRefGoogle Scholar
  15. N. Li Jeon, H. Baskaran, S.K. Dertinger, G.M. Whitesides and L. Van de Waterand M. Toner, Nat Biotechnol 20, 826–830. Epub 2002 Jul 2001 (2002).Google Scholar
  16. L.A. Matheson and R.S. Labowand J.P. Santerre, J Biomed Mater Res 61, 505–513 (2002).CrossRefGoogle Scholar
  17. J.B. Matthews, T.R. Green, M.H. Stone, B.M. Wroblewski and J. Fisherand E. Ingham, Biomaterials 21, 2033–2044 (2000).CrossRefGoogle Scholar
  18. S.B. Milam and R.J. Mackayand L.A. Skelley, Cornell Vet 82, 435–446 (1992).Google Scholar
  19. W. Mitchell, J. Bridget Matthews, M.H. Stone and J. Fisherand E. Ingham, Biomaterials 24, 737–748 (2003).CrossRefGoogle Scholar
  20. D.D. Morris, J.N. Moore and K. Fischerand R.L. Tarleton, Circ Shock 30, 229–236 (1990).Google Scholar
  21. T. Mosmann J Immunol Methods 65, 55–63 (1983).CrossRefGoogle Scholar
  22. K. Ohki, F. Amano and S. Yamamotoand O. Kohashi, Immunol Cell Biol 77, 143–152 (1999).CrossRefGoogle Scholar
  23. C. Schmidt, G. Steinbach, R. Decking and L.E. Claesand A.A. Ignatius, Biomaterials 24, 4191–4196 (2003).CrossRefGoogle Scholar
  24. P. Sivashanmugam and L. Tangand Y. Daaka, J Biol Chem 279, 21154–21159 (2004).CrossRefGoogle Scholar
  25. M.C. Trindade, M. Lind, D. Sun, D.J. Schurman and S.B. Goodmanand R.L. Smith, Biomaterials 22, 253–259 (2001).Google Scholar
  26. W. Wang, D.J.P. Ferguson, J.M.W. Quinn and A. Simpsonand N.A. Athanasou, Journal of Bone and Joint Surgery-British Volume 79B, 849–856 (1997).Google Scholar
  27. P.H. Wooley, R. Morren, J. Andary, S. Sud and S.Y. YangL. Mayton, D. Markel, A. Sieving, and S. Nasser, Biomaterials 23, 517–526 (2002).CrossRefGoogle Scholar
  28. P.L. Yao, Y.C. Lin, C.H. Wang, Y.C. Huang and W.Y. LiaoS.S. Wang, J.J. Chen, and P.C. Yang, Am J Respir Cell Mol Biol 32, 540–547 (2005).CrossRefGoogle Scholar
  29. H. Yasuda, N. Shima, N. Nakagawa, K. Yamaguchi and M. KinosakiM. Goto, S.I. Mochizuki, E. Tsuda, T. Morinaga, N. Udagawa, N. Takahashi, T. Suda, and K. Higashio, Bone 25, 109–113 (1999).CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Research Center for Applied SciencesAcademia SinicaTaiwan
  2. 2.Institute of Biomedical EngineeringNational Taiwan UniversityTaiwan

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