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

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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.

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References

  • M.A. Attawia and J.J. Nicholsonand C.T. Laurencin, Clin Orthop 230–236 (1999).

  • J.Y. Cheng, C.W. Wei and K.H. Hsuand T.H. Young, Sensors and Actuators B: Chemical 99, 186–196 (2004).

    Google Scholar 

  • H. Gelb, H.R. Schumacher, J. Cuckler and P. Ducheyneand D.G. Baker, J Orthop Res 12, 83–92 (1994).

    Google Scholar 

  • 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 

  • 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).

    Article  Google Scholar 

  • T.R. Green, J. Fisher, J.B. Matthews and M.H. Stoneand E. Ingham, J Biomed Mater Res 53, 490–497 (2000).

    Article  Google Scholar 

  • S.M. Horowitz, B.P. Rapuano and J.M. Laneand A.H. Burstein, Calcif Tissue Int 54, 320–324 (1994).

    Article  Google Scholar 

  • 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 

  • E. Ingham, T.R. Green, M.H. Stone, R. Kowalski and N. Watkinsand J. Fisher, Biomaterials 21, 1005–1013 (2000).

    Article  Google Scholar 

  • Y. Jiang, C.K. Mehta and T.Y. Hsuand F.F. Alsulaimani, Infect Immun 70, 3143–3148 (2002).

    Google Scholar 

  • F.Y. Jin, C. Nathan and D. Radziochand A. Ding, Cell 88, 417–426 (1997).

    Article  Google Scholar 

  • T. Kirikae, F.U. Schade, F. Kirikae and E.T. Rietscheland D.C. Morrison, J Immunol 151, 2742–2752 (1993).

    Google Scholar 

  • P. Lavigne, Q. Shi, F.C. Jolicoeur, J.P. Pelletier, J. Martel-Pelletier and J.C. Fernandes, Osteoarthritis Cartilage 10, 898–904 (2002).

    Article  Google Scholar 

  • P. Lavigne, Q. Shi, D. Lajeunesse and F. Dehnadeand J.C. Fernandes, Bone 34, 478–486 (2004).

    Article  Google Scholar 

  • 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).

  • L.A. Matheson and R.S. Labowand J.P. Santerre, J Biomed Mater Res 61, 505–513 (2002).

    Article  Google Scholar 

  • J.B. Matthews, T.R. Green, M.H. Stone, B.M. Wroblewski and J. Fisherand E. Ingham, Biomaterials 21, 2033–2044 (2000).

    Article  Google Scholar 

  • S.B. Milam and R.J. Mackayand L.A. Skelley, Cornell Vet 82, 435–446 (1992).

    Google Scholar 

  • W. Mitchell, J. Bridget Matthews, M.H. Stone and J. Fisherand E. Ingham, Biomaterials 24, 737–748 (2003).

    Article  Google Scholar 

  • D.D. Morris, J.N. Moore and K. Fischerand R.L. Tarleton, Circ Shock 30, 229–236 (1990).

    Google Scholar 

  • T. Mosmann J Immunol Methods 65, 55–63 (1983).

    Article  Google Scholar 

  • K. Ohki, F. Amano and S. Yamamotoand O. Kohashi, Immunol Cell Biol 77, 143–152 (1999).

    Article  Google Scholar 

  • C. Schmidt, G. Steinbach, R. Decking and L.E. Claesand A.A. Ignatius, Biomaterials 24, 4191–4196 (2003).

    Article  Google Scholar 

  • P. Sivashanmugam and L. Tangand Y. Daaka, J Biol Chem 279, 21154–21159 (2004).

    Article  Google Scholar 

  • M.C. Trindade, M. Lind, D. Sun, D.J. Schurman and S.B. Goodmanand R.L. Smith, Biomaterials 22, 253–259 (2001).

    Google Scholar 

  • 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 

  • 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).

    Article  Google Scholar 

  • 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).

    Article  Google Scholar 

  • 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).

    Article  Google Scholar 

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Correspondence to Ji-Yen Cheng.

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Wei, CW., Cheng, JY. & Young, TH. Elucidating in vitro cell-cell interaction using a microfluidic coculture system. Biomed Microdevices 8, 65–71 (2006). https://doi.org/10.1007/s10544-006-6384-8

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  • DOI: https://doi.org/10.1007/s10544-006-6384-8

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