Isolation and perivascular localization of mesenchymal stem cells from mouse brain.

Isolation and perivascular localization of mesenchymal stem cells from mouse brain.
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DOI:
10.1227/01.neu.0000377859.06219.78
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发表时间:
2010-09
期刊:
影响因子:
4.8
通讯作者:
Lang FF
Lang FF
中科院分区:
医学1区
文献类型:
--
作者:
Kang SG;Shinojima N;Hossain A;Gumin J;Yong RL;Colman H;Marini F;Andreeff M;Lang FF

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虽然最初是从骨髓中分离出来的,但最近在其他组织中发现了间充质干细胞(MSC)。然而,对大脑中的MSC知之甚少。目的:确定正常脑组织中具有间充质干细胞特征的细胞存在的程度,并确定这些细胞在脑中的位置。根据用于培养骨髓来源的MSC(BM-MSC)的相同方法培养来自小鼠脑的单细胞悬浮液。这些脑源性细胞通过荧光激活细胞分选术分析与BM-MSC相关的表面标志物(干细胞抗原1 [Sca-1+]、CD 9+、CD 45 −、CD 11b −和CD 31 −)。将脑源性细胞暴露于间充质分化条件。为了确定这些细胞在脑内的位置,通过对Sca-1、CD 31和神经/神经胶质抗原2进行免疫染色来分析正常脑的切片。鉴定出形态学上类似于小鼠BM-MSC的细胞,并将其称为脑源性MSC(Br-MSC)。活化细胞分选表明,分离的细胞具有与BM-MSC相似的表面标志物特征,即Sca-1+、CD 9+、CD 45-和CD 11b-。与BM-MSCs一样,Br-MSCs能够分化为脂肪细胞、骨细胞和软骨细胞。免疫染色表明,Sca-1+ Br-MSCs位于血管周围,可能代表祖细胞,作为脑内间充质成分(如周细胞)的来源。我们的结果表明,类似于BM-MSCs的细胞存在于大脑中。这些Br-MSCs似乎位于血管龛内,并可能提供该龛的间充质成分。由于MSC可能是对组织损伤的细胞反应的一部分,因此Br-MSC可能代表诸如中风、创伤和肿瘤发生的病理过程的治疗中的靶点。
Although originally isolated from the bone marrow, mesenchymal stem cells (MSCs) have recently been detected in other tissues. However, little is known about MSCs in the brain. To determine the extent to which cells with the features of MSCs exist in normal brain tissue and to determine the location of these cells in the brain. Single-cell suspensions from mouse brains were cultured according to the same methods used for culturing bone marrow–derived MSCs (BM-MSCs). These brain-derived cells were analyzed by fluorescence-activated cell sorting for surface markers associated with BM-MSCs (stem cell antigen 1 [Sca-1+], CD9+, CD45−, CD11b−, and CD31−). Brain-derived cells were exposed to mesenchymal differentiation conditions. To determine the locations of these cells within the brain, sections of normal brains were analyzed by immunostaining for Sca-1, CD31, and nerve/glial antigen 2. Cells morphologically similar to mouse BM-MSCs were identified and called brain-derived MSCs (Br-MSCs). Fluorescence-activated cell sorting indicated that the isolated cells had a surface marker profile similar to BM-MSCs, ie, Sca-1+, CD9+, CD45−, and CD11b−. Like BM-MSCs, Br-MSCs were capable of differentiation into adipocytes, osteocytes, and chondrocytes. Immunostaining indicated that Sca-1+ Br-MSCs are located around blood vessels and may represent progenitor cells that serve as a source of mesenchymal elements (eg, pericytes) within the brain. Our results indicate that cells similar to BM-MSCs exist in the brain. These Br-MSCs appear to be located within the vascular niche and may provide the mesenchymal elements of this niche. Because MSCs may be part of the cellular response to tissue injury, Br-MSCs may represent targets in the therapy of pathological processes such as stroke, trauma, and tumorigenesis.