Establishment of autaptic culture with human-induced pluripotent stem cell-derived astrocytes
Kouya Uchino,
Yasuyoshi Tanaka,
Sayaka Kawaguchi,
Kaori Kubota,
Takuya Watanabe,
Shutaro Katsurabayashi,
Shinichi Hirose,
Katsunori Iwasaki
Affiliations
Kouya Uchino
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Yasuyoshi Tanaka
Department of Advanced Pharmacology, Daiichi University of Pharmacy, 22-1 Tamagawa-machi, Minami-ku, Fukuoka 815-8511, Japan; iONtarget, Co., Inc., 1-3-70-5805 Momochihama, Sawara-ku, Fukuoka 814-0006, Japan; Research Institute for the Molecular Pathogeneses of Epilepsy, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Sayaka Kawaguchi
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Kaori Kubota
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Takuya Watanabe
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Shutaro Katsurabayashi
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan; Research Institute for the Molecular Pathogeneses of Epilepsy, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan; Corresponding author
Shinichi Hirose
iONtarget, Co., Inc., 1-3-70-5805 Momochihama, Sawara-ku, Fukuoka 814-0006, Japan; Research Institute for the Molecular Pathogeneses of Epilepsy, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan; General Medical Research Center, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Katsunori Iwasaki
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
Summary: Although astrocytes are involved in the pathogenesis of CNS diseases, how they induce synaptic abnormalities is unclear. Currently, in vitro pathological astrocyte cultures or animal models do not reproduce human disease phenotypes accurately. Induced pluripotent stem cells (iPSCs) are replacing animal models in pathological studies. We developed an autaptic culture (AC) system containing single neuron cultures grown on microislands of astrocytes. AC with human iPSC-derived astrocytes (HiA) was established. We evaluated the effect of astrocytes on the synaptic functions of human-derived neurons. We found a significantly higher Na+ current amplitude, membrane capacitance, and number of synapses, as well as longer dendrites, in HiAACs compared with neuron monocultures. Furthermore, HiAs were involved in the formation and maturation of functional synapses that exhibited excitatory postsynaptic currents. This system can facilitate the study of CNS diseases and advance the development of drugs targeting glial cells.
