Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.
Mol Neurobiol. 2018 Jul;55(7):5993-6006. doi: 10.1007/s12035-017-0815-9. Epub 2017 Nov 11.
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.
虽然周细胞环绕着人体的微血管内皮细胞,但它们在大脑中的覆盖率最高。脑周细胞积极参与各种大脑功能,包括血脑屏障 (BBB) 的发育和稳定、组织再生和大脑炎症。因此,详细描述脑周细胞的功能特性对于理解大脑生理学和病理生理学的机制基础非常重要。在此,我们报告了一种新的人类脑周细胞系的发展,以下简称人类脑周细胞/条件永生化克隆 37(HBPC/ci37)。这些细胞通过细胞条件永生化方法开发,在 33°C 时表现出优异的增殖能力。然而,当在 37°C 下培养时,HBPC/ci37 细胞表现出分化表型,其特征是形态改变和几种周细胞富集标记物 mRNA 水平的增加,例如血小板衍生生长因子受体 β。还发现 HBPC/ci37 细胞具有体外 BBB 形成和分化为神经元谱系的促进能力。此外,HBPC/ci37 细胞表现出对促炎细胞因子的典型“反应性”脑周细胞特征。总之,我们的结果清楚地表明,HBPC/ci37 细胞具有执行几种关键脑周细胞功能的能力,同时还具有广泛和持续增殖的能力。基于这些发现,可以预期,作为一种独特的人类脑周细胞模型,HBPC/ci37 细胞有可能对理解人类脑周细胞生理学和病理生理学做出重大贡献。