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A New Conditionally Immortalized Human Fetal Brain Pericyte Cell Line: Establishment and Functional Characterization as a Promising Tool for Human Brain Pericyte Studies

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Abstract

While pericytes wrap around microvascular endothelial cells throughout the human body, their highest coverage rate is found in the brain. Brain pericytes actively contribute to various brain functions, including the development and stabilization of the blood-brain barrier (BBB), tissue regeneration, and brain inflammation. Accordingly, detailed characterization of the functional nature of brain pericytes is important for understanding the mechanistic basis of brain physiology and pathophysiology. Herein, we report on the development of a new human brain pericyte cell line, hereafter referred to as the human brain pericyte/conditionally immortalized clone 37 (HBPC/ci37). Developed via the cell conditionally immortalization method, these cells exhibited excellent proliferative ability at 33 °C. However, when cultured at 37 °C, HBPC/ci37 cells showed a differentiated phenotype that was marked by morphological alterations and increases in several pericyte-enriched marker mRNA levels, such as platelet-derived growth factor receptor β. It was also found that HBPC/ci37 cells possessed the facilitative ability of in vitro BBB formation and differentiation into a neuronal lineage. Furthermore, HBPC/ci37 cells exhibited the typical “reactive” features of brain pericytes in response to pro-inflammatory cytokines. To summarize, our results clearly demonstrate that HBPC/ci37 cells possess the ability to perform several key brain pericyte functions while also showing the capacity for extensive and continuous proliferation. Based on these findings, it can be expected that, as a unique human brain pericyte model, HBPC/ci37 cells have the potential to contribute to significant advances in the understanding of human brain pericyte physiology and pathophysiology.

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Acknowledgements

We would like to thank Dr. Mari Hashimoto (Research Center for Molecular Medicine of the Austrian Academy of Sciences) for providing the technical support to this study.

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Author notes

  1. Kosuke Saito

    Present address: Division of Medical Safety Science, National Institute of Health Sciences, Tokyo, 158-8501, Japan

Authors and Affiliations

  1. Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan

    Kenta Umehara, Yuchen Sun, Keita Kitamura, Kosuke Saito, Kan Chiba, Hidetaka Akita & Tomomi Furihata

  2. Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan

    Satoshi Hiura, Koki Hamada & Motoyuki Itoh

  3. Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan

    Motohiko Oshima & Atsushi Iwama

  4. Department of Pharmacology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan

    Naohiko Anzai & Tomomi Furihata

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  1. Kenta Umehara
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Correspondence to Tomomi Furihata.

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The Ethics Committee of the Chiba University (Chiba, Japan) approved the use of human cells in this study.

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Umehara, K., Sun, Y., Hiura, S. et al. A New Conditionally Immortalized Human Fetal Brain Pericyte Cell Line: Establishment and Functional Characterization as a Promising Tool for Human Brain Pericyte Studies. Mol Neurobiol 55, 5993–6006 (2018). https://doi.org/10.1007/s12035-017-0815-9

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