Induction of Mesoderm and Neural Crest-Derived Pericytes from Human Pluripotent Stem Cells to Study Blood-Brain Barrier Interactions
Induction of Mesoderm and Neural Crest-Derived Pericytes from Human Pluripotent Stem Cells to Study Blood-Brain Barrier Interactions
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DOI：
10.1016/j.stemcr.2019.01.005
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发表时间：
2019-03-05
影响因子：
5.9
通讯作者：
Inlay, Matthew A.
中科院分区：
文献类型：
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作者：
Faal, Tannaz;Phan, Duc T. T.;Inlay, Matthew A.
在中枢神经系统中，血管周细胞(“周细胞”)与内皮细胞结合，调节血脑屏障(BBB)功能所必需的紧密连接的形成。血脑屏障通过调节营养物质和毒素流入和流出大脑来保护中枢神经系统。血脑屏障功能障碍与阿尔茨海默病(AD)的进展有关，但周细胞在AD血脑屏障功能障碍中的作用尚不清楚。在发育中的胚胎中，中枢神经周细胞有两个来源：中胚层和神经脊。在这项研究中，我们报告了两种方案，使用中胚层或神经脊中间体，从来自健康和AD患者的诱导多能干细胞(IPSC)系中生成脑特异性周细胞样细胞。IPSC来源的周细胞能够稳定表达周细胞表面标志和脑特异性基因，并且在功能上能够增加血管形成和内皮屏障特性。
In the CNS, perivascular cells ("pericytes") associate with endothelial cells to mediate the formation of tight junctions essential to the function of the blood-brain barrier (BBB). The BBB protects the CNS by regulating the flow of nutrients and toxins into and out of the brain. BBB dysfunction has been implicated in the progression of Alzheimer's disease (AD), but the role of pericytes in BBB dysfunction in AD is not well understood. In the developing embryo, CNS pericytes originate from two sources: mesoderm and neural crest. In this study, we report two protocols using mesoderm or neural crest intermediates, to generate brain-specific pericyte-like cells from induced pluripotent stem cell (iPSC) lines created from healthy and AD patients. iPSC-derived pericytes display stable expression of pericyte surface markers and brain-specific genes and are functionally capable of increasing vascular tube formation and endothelial barrier properties.