Differentiated HASTR/ci35 cells: A promising in vitro human astrocyte model for facilitating CNS drug development studies
Astrocytes have shown longstanding promise as therapeutic targets for various central nervous system diseases. To facilitate drug development targeting astrocytes, we have recently developed a new conditionally immortalized human astrocyte cell line, termed HASTR/ci35 cells. In this study, in order...
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doaj-d2b8e5e3c44f498381040234818166c52020-11-25T01:47:07ZengElsevierJournal of Pharmacological Sciences1347-86132018-08-011374350358Differentiated HASTR/ci35 cells: A promising in vitro human astrocyte model for facilitating CNS drug development studiesKeita Kitamura0Ryo Ito1Kenta Umehara2Hanae Morio3Kosuke Saito4Shota Suzuki5Mari Hashimoto6Yoshiro Saito7Naohiko Anzai8Hidetaka Akita9Kan Chiba10Tomomi Furihata11Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan; Department of Pharmacology, Graduate School of Medicine, Chiba University, Chiba 260-8670, JapanDivision of Medical Safety Science, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, JapanLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanDivision of Medical Safety Science, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki 210-9501, JapanDepartment of Pharmacology, Graduate School of Medicine, Chiba University, Chiba 260-8670, JapanLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanLaboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan; Department of Pharmacology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Corresponding author. Department of Pharmacology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan. Tel/Fax: +81 43 226 2051/2052.Astrocytes have shown longstanding promise as therapeutic targets for various central nervous system diseases. To facilitate drug development targeting astrocytes, we have recently developed a new conditionally immortalized human astrocyte cell line, termed HASTR/ci35 cells. In this study, in order to further increase their chances to contribute to various astrocyte studies, we report on the development of a culture method that improves HASTR/ci35 cell differentiation status and provide several proofs related to their astrocyte characteristics. The culture method is based on the simultaneous elimination of serum effects and immortalization signals. The results of qPCR showed that the culture method significantly enhanced several astrocyte marker gene expression levels. Using the differentiated HASTR/ci35, we examined their response profiles to nucleotide treatment and inflammatory stimuli, along with their membrane fatty acid composition. Consequently, we found that they responded to ADP or UTP treatment with a transient increase of intracellular Ca2+ concentration, and that they could show reactive response to interleukin-1β treatments. Furthermore, the membrane phospholipids of the cells were enriched with polyunsaturated fatty acids. To summarize, as a unique human astrocyte model carrying the capability of a differentiation induction properties, HASTR/ci35 cells are expected to contribute substantially to astrocyte-oriented drug development studies. Keywords: Astrocytes, Drug development, Immortalized cells, In vitro model, Central nervous systemhttp://www.sciencedirect.com/science/article/pii/S1347861318301294 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Keita Kitamura Ryo Ito Kenta Umehara Hanae Morio Kosuke Saito Shota Suzuki Mari Hashimoto Yoshiro Saito Naohiko Anzai Hidetaka Akita Kan Chiba Tomomi Furihata |
spellingShingle |
Keita Kitamura Ryo Ito Kenta Umehara Hanae Morio Kosuke Saito Shota Suzuki Mari Hashimoto Yoshiro Saito Naohiko Anzai Hidetaka Akita Kan Chiba Tomomi Furihata Differentiated HASTR/ci35 cells: A promising in vitro human astrocyte model for facilitating CNS drug development studies Journal of Pharmacological Sciences |
author_facet |
Keita Kitamura Ryo Ito Kenta Umehara Hanae Morio Kosuke Saito Shota Suzuki Mari Hashimoto Yoshiro Saito Naohiko Anzai Hidetaka Akita Kan Chiba Tomomi Furihata |
author_sort |
Keita Kitamura |
title |
Differentiated HASTR/ci35 cells: A promising in vitro human astrocyte model for facilitating CNS drug development studies |
title_short |
Differentiated HASTR/ci35 cells: A promising in vitro human astrocyte model for facilitating CNS drug development studies |
title_full |
Differentiated HASTR/ci35 cells: A promising in vitro human astrocyte model for facilitating CNS drug development studies |
title_fullStr |
Differentiated HASTR/ci35 cells: A promising in vitro human astrocyte model for facilitating CNS drug development studies |
title_full_unstemmed |
Differentiated HASTR/ci35 cells: A promising in vitro human astrocyte model for facilitating CNS drug development studies |
title_sort |
differentiated hastr/ci35 cells: a promising in vitro human astrocyte model for facilitating cns drug development studies |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2018-08-01 |
description |
Astrocytes have shown longstanding promise as therapeutic targets for various central nervous system diseases. To facilitate drug development targeting astrocytes, we have recently developed a new conditionally immortalized human astrocyte cell line, termed HASTR/ci35 cells. In this study, in order to further increase their chances to contribute to various astrocyte studies, we report on the development of a culture method that improves HASTR/ci35 cell differentiation status and provide several proofs related to their astrocyte characteristics. The culture method is based on the simultaneous elimination of serum effects and immortalization signals. The results of qPCR showed that the culture method significantly enhanced several astrocyte marker gene expression levels. Using the differentiated HASTR/ci35, we examined their response profiles to nucleotide treatment and inflammatory stimuli, along with their membrane fatty acid composition. Consequently, we found that they responded to ADP or UTP treatment with a transient increase of intracellular Ca2+ concentration, and that they could show reactive response to interleukin-1β treatments. Furthermore, the membrane phospholipids of the cells were enriched with polyunsaturated fatty acids. To summarize, as a unique human astrocyte model carrying the capability of a differentiation induction properties, HASTR/ci35 cells are expected to contribute substantially to astrocyte-oriented drug development studies. Keywords: Astrocytes, Drug development, Immortalized cells, In vitro model, Central nervous system |
url |
http://www.sciencedirect.com/science/article/pii/S1347861318301294 |
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