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

被引:0
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作者
Kenta Umehara
Yuchen Sun
Satoshi Hiura
Koki Hamada
Motoyuki Itoh
Keita Kitamura
Motohiko Oshima
Atsushi Iwama
Kosuke Saito
Naohiko Anzai
Kan Chiba
Hidetaka Akita
Tomomi Furihata
机构
[1] Chiba University,Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences
[2] Chiba University,Department of Biochemistry, Graduate School of Pharmaceutical Sciences
[3] Chiba University,Department of Cellular and Molecular Medicine, Graduate School of Medicine
[4] National Institute of Health Sciences,Division of Medical Safety Science
[5] Chiba University,Department of Pharmacology, Graduate School of Medicine
来源
Molecular Neurobiology | 2018年 / 55卷
关键词
Pericytes; Blood-brain barrier; Conditionally immortalized cells; In vitro model; Multipotency; Brain inflammation;
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学科分类号
摘要
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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页码:5993 / 6006
页数:13
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