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http://dx.doi.org/10.14348/molcells.2014.0137

Monitoring the Differentiation and Migration Patterns of Neural Cells Derived from Human Embryonic Stem Cells Using a Microfluidic Culture System  

Lee, Nayeon (CHA Stem Cell Institute, CHA University)
Park, Jae Woo (Division of World Class University Multiscale Mechanical Design, School of Mechanical and Aerospace Engineering, Seoul National University)
Kim, Hyung Joon (Division of World Class University Multiscale Mechanical Design, School of Mechanical and Aerospace Engineering, Seoul National University)
Yeon, Ju Hun (Division of World Class University Multiscale Mechanical Design, School of Mechanical and Aerospace Engineering, Seoul National University)
Kwon, Jihye (CHA Stem Cell Institute, CHA University)
Ko, Jung Jae (CHA Stem Cell Institute, CHA University)
Oh, Seung-Hun (CHA Stem Cell Institute, CHA University)
Kim, Hyun Sook (CHA Stem Cell Institute, CHA University)
Kim, Aeri (CHA Stem Cell Institute, CHA University)
Han, Baek Soo (Research Center for Integrated Cellulomics, Korea Research Institute of Bioscience and Biotechnology)
Lee, Sang Chul (Research Center for Integrated Cellulomics, Korea Research Institute of Bioscience and Biotechnology)
Jeon, Noo Li (Division of World Class University Multiscale Mechanical Design, School of Mechanical and Aerospace Engineering, Seoul National University)
Song, Jihwan (CHA Stem Cell Institute, CHA University)
Abstract
Microfluidics can provide unique experimental tools to visualize the development of neural structures within a microscale device, which is followed by guidance of neurite growth in the axonal isolation compartment. We utilized microfluidics technology to monitor the differentiation and migration of neural cells derived from human embryonic stem cells (hESCs). We co-cultured hESCs with PA6 stromal cells, and isolated neural rosette-like structures, which subsequently formed neurospheres in suspension culture. Tuj1-positive neural cells, but not nestin-positive neural precursor cells (NPCs), were able to enter the microfluidics grooves (microchannels), suggesting that neural cell-migratory capacity was dependent upon neuronal differentiation stage. We also showed that bundles of axons formed and extended into the microchannels. Taken together, these results demonstrated that microfluidics technology can provide useful tools to study neurite outgrowth and axon guidance of neural cells, which are derived from human embryonic stem cells.
Keywords
axons; human embryonic stem cells; microfluidics; migration; neural differentiation;
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1 Reubinoff, B.E., Pera, M.F., Fong, C.Y., Trounson, A., and Bongso, A. (2000). Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat. Biotechnol. 18, 399-404.   DOI   ScienceOn
2 Rhee, S.W., Taylor, A.M., Tu, C.H., Cribbs, D.H., Cotman, C.W., and Jeon, N.L. (2005). Patterned cell culture inside microfluidic devices. Lab. Chip 2005 5, 102-107.   DOI   ScienceOn
3 Shin, H.S., Kim, H.J., Min, S.K., Kim, S.H., Lee, B.M., and Jeon, N.L. (2010). Compartmental culture of embryonic stem cell-derived neurons in microfluidic devices for use in axonal biology. Biotechnol. Lett. 32, 1063-1070.   DOI   ScienceOn
4 Taylor, A.M., Rhee, S.W., and Jeon, N.L. (2006). Microfluidic chambers for cell migration and neuroscience research. Methods Mol. Biol. 321, 167-177.
5 Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S., and Jones, J.M. (1998). Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147.   DOI   ScienceOn
6 Jeon, I., Lee, N., Li, J.Y., Park, I.H., Park, S., Moon, J., Shim, S.H., Choi, C., Chang, D.J., Kwon, J., et al. (2012). Neural properties, in vivo effects and pathology of a Huntington's disease patient-derived induced pluripotent stem cells. Stem Cells 30, 2054-2062.   DOI   ScienceOn
7 Kim, H.J., Park, J.W., Byun, J.H., Vahidi, B., Rhee, S.W., and Jeon, N.L. (2012). Integrated microfluidics platforms for investigating injury and regeneration of CNS axons. Ann. Biomed. Eng. 40, 1268-1276.   DOI   ScienceOn
8 Kosik, K.S., and Finch, E.A. (1987). MAP2 and Tau segregate into dendrite and axon domains after the elaboration of morphologically distinct neuritis: an immunocytochemical study of cultured rat cerebrum. J. Neurosci. 7, 3142-3153.
9 Lee, N., Choi, C., Jeon, I., and Song, J. (2009). Differentiation of GABAergic neurons from human embryonic stem cells. Tissue Eng. Regen. Med. 6, 1359-1365.
10 Millet, L.J., and Gillette, M.U. (2012). New perspectives on neuronal development via microfluidic environments. Trends Neurosci. 35, 752-761.   DOI   ScienceOn
11 Millet, L.J., Stewart, M.E., Nuzzo, R.G., and Gillette, M.U. (2010). Guiding neuron development with planar surface gradients of substrate cues deposited using microfluidic devices. Lab. Chip 10, 1525-1535.   DOI   ScienceOn
12 Park, J.W., Vahidi, B., Taylor, A.M., Rhee, S.W., and Jeon, N.L. (2006). Microfluidic culture platform for neuroscience research. Nat. Protoc. 1, 2128-2136.   DOI   ScienceOn
13 Park, J.W., Kim, H.J., Byun, J.H., Ryu, H.R., and Jeon, N.L. (2009). Novel microfluidic platform for culturing neurons: culturing and biochemical analysis of neuronal components. Biotechnol. J. 4, 1573-1577.   DOI   ScienceOn
14 Park, J.W., Kim, H.J., Kang, M.W., and Jeon, N.L. (2013). Advances in microfluidics-based experimental methods for neuroscience research. Lab. Chip 13, 509-521.   DOI   ScienceOn
15 Bellin, M., Marchetto, M.C., Gage, F.H., and Mummery, C.L. (2012). Induced pluripotent stem cells: the new patient? Nat. Rev. Mol. Cell. Biol. 13, 713-726.
16 Blow, N. (2008). Stem cells: in search of common ground. Nature 451, 855-858.   DOI   ScienceOn
17 Cohen, M.S., Bas Orth, C., Kim, H.J., Jeon, N.L., and Jaffrey, S,R. (2011). Neurotrophin-mediated dendrite-to-nucleus signaling revealed by microfluidic compartmentalization of dendrites. Proc. Natl. Acad. Sci. USA 108, 11246-11251.   DOI   ScienceOn
18 Breslauer, D.N., Lee, P.J., and Lee LP. (2006). Microfluidics-based systems biology. Mol. Biosyst. 2, 97-112.   DOI   ScienceOn
19 Hamon, M., and Hong, J.W. (2013). New tools and new biology: recent miniaturized systems for molecular and cellular biology. Mol. Cells 36, 485-506.   DOI