caa a22 4500 605480133 CHVBK 20210128100413.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s10544-015-9997-y doi (NATIONALLICENCE)springer-10.1007/s10544-015-9997-y Recording axonal conduction to evaluate the integration of pluripotent cell-derived neurons into a neuronal network [Elektronische Daten] [Kenta Shimba, Koji Sakai, Yuzo Takayama, Kiyoshi Kotani, Yasuhiko Jimbo] Stem cell transplantation is a promising therapy to treat neurodegenerative disorders, and a number of in vitro models have been developed for studying interactions between grafted neurons and the host neuronal network to promote drug discovery. However, methods capable of evaluating the process by which stem cells integrate into the host neuronal network are lacking. In this study, we applied an axonal conduction-based analysis to a co-culture study of primary and differentiated neurons. Mouse cortical neurons and neuronal cells differentiated from P19 embryonal carcinoma cells, a model for early neural differentiation of pluripotent stem cells, were co-cultured in a microfabricated device. The somata of these cells were separated by the co-culture device, but their axons were able to elongate through microtunnels and then form synaptic contacts. Propagating action potentials were recorded from these axons by microelectrodes embedded at the bottom of the microtunnels and sorted into clusters representing individual axons. While the number of axons of cortical neurons increased until 14days in vitro and then decreased, those of P19 neurons increased throughout the culture period. Network burst analysis showed that P19 neurons participated in approximately 80% of the bursting activity after 14days in vitro. Interestingly, the axonal conduction delay of P19 neurons was significantly greater than that of cortical neurons, suggesting that there are some physiological differences in their axons. These results suggest that our method is feasible to evaluate the process by which stem cell-derived neurons integrate into a host neuronal network. Springer Science+Business Media New York, 2015 P19 embryonal carcinoma cells nationallicence Stem cells nationallicence Neuronal networks nationallicence Axonal conduction nationallicence Microelectrode array nationallicence Shimba Kenta Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, University of Tokyo, Room 1122, Faculty of Engineering Bldg., 14, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, Japan aut Sakai Koji Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, University of Tokyo, Room 1122, Faculty of Engineering Bldg., 14, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, Japan aut Takayama Yuzo Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 4, 1-1-1 Higashi, 305-8562, Tsukuba, Ibaraki, Japan aut Kotani Kiyoshi Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, 153-8904, Tokyo, Japan aut Jimbo Yasuhiko Department of Precision Engineering, School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, Japan aut Biomedical Microdevices Springer US; http://www.springer-ny.com 17/5(2015-10-01), 1-10 1387-2176 17:5<1 2015 17 10544 https://doi.org/10.1007/s10544-015-9997-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10544-015-9997-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shimba Kenta Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, University of Tokyo, Room 1122, Faculty of Engineering Bldg., 14, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, Japan aut NATIONALLICENCE 700 1- Sakai Koji Department of Human and Engineered Environmental Studies, Graduate School of Frontier Sciences, University of Tokyo, Room 1122, Faculty of Engineering Bldg., 14, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, Japan aut NATIONALLICENCE 700 1- Takayama Yuzo Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 4, 1-1-1 Higashi, 305-8562, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Kotani Kiyoshi Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, 153-8904, Tokyo, Japan aut NATIONALLICENCE 700 1- Jimbo Yasuhiko Department of Precision Engineering, School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, Japan aut NATIONALLICENCE 773 0- Biomedical Microdevices Springer US; http://www.springer-ny.com 17/5(2015-10-01), 1-10 1387-2176 17:5<1 2015 17 10544