Sakuma Rika, Kawahara Maiko, Nakano-Doi Akiko, Takahashi Ai, Tanaka Yasue, Narita Aya, Kuwahara-Otani Sachi, Hayakawa Tetsu, Yagi Hideshi, Matsuyama Tomohiro, Nakagomi Takayuki
Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan.
Graduate School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan.
J Neuroinflammation. 2016 Mar 7;13(1):57. doi: 10.1186/s12974-016-0523-9.
Microglia are the resident macrophage population of the central nervous system (CNS) and play essential roles, particularly in inflammation-mediated pathological conditions such as ischemic stroke. Increasing evidence shows that the population of vascular cells located around the blood vessels, rather than circulating cells, harbor stem cells and that these resident vascular stem cells (VSCs) are the likely source of some microglia. However, the precise traits and origins of these cells under pathological CNS conditions remain unclear.
In this study, we used a mouse model of cerebral infarction to investigate whether reactive pericytes (PCs) acquire microglia-producing VSC activity following ischemia.
We demonstrated the localization of ionized calcium-binding adaptor molecule 1 (Iba1)-expressing microglia to perivascular regions within ischemic areas. These cells expressed platelet-derived growth factor receptor-β (PDGFRβ), a hallmark of vascular PCs. PDGFRβ(+) PCs isolated from ischemic, but not non-ischemic, areas expressed stem/undifferentiated cell markers and subsequently differentiated into various cell types, including microglia-like cells with phagocytic capacity.
The study results suggest that vascular PCs acquire multipotent VSC activity under pathological conditions and may thus be a novel source of microglia.
小胶质细胞是中枢神经系统(CNS)中的常驻巨噬细胞群体,发挥着重要作用,尤其是在诸如缺血性中风等炎症介导的病理状况中。越来越多的证据表明,位于血管周围的血管细胞群体而非循环细胞含有干细胞,并且这些常驻血管干细胞(VSCs)可能是某些小胶质细胞的来源。然而,在病理性中枢神经系统条件下这些细胞的确切特征和起源仍不清楚。
在本研究中,我们使用脑梗死小鼠模型来研究反应性周细胞(PCs)在缺血后是否获得产生小胶质细胞的VSC活性。
我们证明了表达离子钙结合衔接分子1(Iba1)的小胶质细胞定位于缺血区域内的血管周围区域。这些细胞表达血小板衍生生长因子受体-β(PDGFRβ)——血管PCs的一个标志。从缺血区域而非非缺血区域分离的PDGFRβ(+)PCs表达干细胞/未分化细胞标志物,随后分化为各种细胞类型,包括具有吞噬能力的小胶质细胞样细胞。
研究结果表明,血管PCs在病理条件下获得多能VSC活性,因此可能是小胶质细胞的一个新来源。