Induced pluripotent stem cell‐based assays recapture multiple properties of human astrocytes

Author:

Nonaka Hideki12,Kondo Takayuki134,Suga Mika13,Yamanaka Ryu2,Sagara Yukako13,Tsukita Kayoko13,Mitsutomi Naoko2,Homma Kengo2,Saito Ryuta2,Miyoshi Fumihiko2,Ohzeki Hiromitsu2,Okuyama Masahiro2,Inoue Haruhisa134ORCID

Affiliation:

1. iPSC‐based Drug Discovery and Development Team, RIKEN BioResource Research Center (BRC) Kyoto Japan

2. Mitsubishi Tanabe Pharma Corporation Yokohama Japan

3. Center for iPS Cell Research and Application (CiRA) Kyoto University Kyoto Japan

4. Medical‐risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP) Kyoto Japan

Abstract

AbstractThe majority of the population of glial cells in the central nervous system consists of astrocytes, and impairment of astrocytes causes various disorders. It is useful to assess the multiple astrocytic properties in order to understand their complex roles in the pathophysiology. Although we can differentiate human astrocytes from induced pluripotent stem cells (iPSCs), it remains unknown how we can analyse and reveal the multiple properties of astrocytes in complexed human disease conditions. For this purpose, we tested astrocytic differentiation protocols from feeder‐free iPSCs based on the previous method with some modifications. Then, we set up extra‐ and intracellular assessments of iPSC‐derived astrocytes by testing cytokine release, calcium influx, autophagy induction and migration. The results led us to analytic methods with conditions in which iPSC‐derived astrocytes behave as in vivo. Finally, we applied these methods for modelling an astrocyte‐related disease, Alexander disease. An analytic system using iPSC‐derived astrocytes could be used to recapture complexities in human astrocyte diseases.

Funder

Japan Agency for Medical Research and Development

Uehara Memorial Foundation

Japan Society for the Promotion of Science

Canon Foundation for Scientific Research

Publisher

Wiley

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