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

doi:10.1016/j.isci.2022.104762

Establishment of autaptic culture with human-induced pluripotent stem cell-derived astrocytes

iScience. 2022 Jul 16;25(8):104762. doi: 10.1016/j.isci.2022.104762. eCollection 2022 Aug 19.

Authors

Kouya Uchino¹, Yasuyoshi Tanaka^{2

3

4}, Sayaka Kawaguchi¹, Kaori Kubota¹, Takuya Watanabe¹, Shutaro Katsurabayashi^{1

4}, Shinichi Hirose^{3

4

5}, Katsunori Iwasaki¹

Affiliations

¹ Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
² Department of Advanced Pharmacology, Daiichi University of Pharmacy, 22-1 Tamagawa-machi, Minami-ku, Fukuoka 815-8511, Japan.
³ iONtarget, Co., Inc., 1-3-70-5805 Momochihama, Sawara-ku, Fukuoka 814-0006, Japan.
⁴ Research Institute for the Molecular Pathogeneses of Epilepsy, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
⁵ General Medical Research Center, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.

Abstract

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.

Keywords: Biological sciences; Cell biology; Cellular neuroscience; Neuroscience; Stem cells research.