A neurovascular-unit-on-a-chip for the evaluation of the restorative potential of stem cell therapies for ischaemic stroke.

A neurovascular-unit-on-a-chip for the evaluation of the restorative potential of stem cell therapies for ischaemic stroke.
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DOI:
10.1038/s41551-021-00744-7
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发表时间:
2021-08
影响因子:
28.1
通讯作者:
Lee W
Lee W
中科院分区:
工程技术1区
文献类型:
--
作者:
Lyu Z;Park J;Kim KM;Jin HJ;Wu H;Rajadas J;Kim DH;Steinberg GK;Lee W

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干细胞移植到缺血脑内的治疗效果主要取决于神经血管单位的反应。在这里,我们报告的发展和适用性的功能性神经血管单元的微流控芯片作为缺血性中风的微生理模型,概括的功能的血脑屏障以及治疗干细胞和宿主细胞(人脑微血管内皮细胞,周细胞,星形胶质细胞,小胶质细胞和神经元)之间的相互作用。我们使用该模型来跟踪一些候选干细胞的浸润,并表征与中风后病理相关的基因的表达水平。我们观察到,每种类型的干细胞表现出独特的神经修复作用,主要是通过支持内源性恢复,而不是通过直接的细胞替代,突触活动的恢复与神经血管单位的结构和功能完整性的恢复相关,而不是与神经元的再生。
The therapeutic efficacy of stem cells transplanted into an ischaemic brain depends primarily on the responses of the neurovascular unit. Here, we report the development and applicability of a functional neurovascular unit on a microfluidic chip as a microphysiological model of ischaemic stroke that recapitulates the function of the blood–brain barrier as well as interactions between therapeutic stem cells and host cells (human brain microvascular endothelial cells, pericytes, astrocytes, microglia and neurons). We used the model to track the infiltration of a number of candidate stem cells and to characterize the expression levels of genes associated with post-stroke pathologies. We observed that each type of stem cell showed unique neurorestorative effects, primarily by supporting endogenous recovery rather than through direct cell replacement, and that the recovery of synaptic activities correlated with the recovery of the structural and functional integrity of the neurovascular unit rather than with the regeneration of neurons.
DOI: 10.1212/wnl.51.3_suppl_3.s44
发表时间: 1998-09-01
期刊: NEUROLOGY
影响因子: 9.9
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