Limitations of the hCMEC/D3 cell line as a model for Aβ clearance by the human blood-brain barrier.
Limitations of the hCMEC/D3 cell line as a model for Aβ clearance by the human blood-brain barrier.
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DOI：
10.1002/jnr.23964
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发表时间：
2017-07
影响因子：
4.2
通讯作者：
Verbeek MM
中科院分区：
文献类型：
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作者：
Biemans EALM;Jäkel L;de Waal RMW;Kuiperij HB;Verbeek MM
阿尔茨海默病和脑淀粉样血管病的特征在于由于血脑屏障（BBB）的清除率降低而导致淀粉样β（Aβ）在脑血管系统中蓄积。然而，Aβ穿过该屏障的确切机制尚未完全阐明。hCMEC/D3细胞系已被表征为BBB的有效模型。在本研究中，我们评价了使用该模型研究Aβ通过BBB的清除率，重点是脑-血定向渗透性。对于大分子，在顶侧至基底侧和相反方向上证实了hCMEC/D3单层的屏障完整性。然而，较小分子的渗透性显著较高，尤其是在基底外侧至顶端方向，在该方向上完全不存在Aβ屏障形成。此外，hCMEC/D3细胞未能形成高TEER，可能是由于紧密连接形成不完全所致。我们得出结论，hCMEC/D3模型在研究Aβ脑清除率方面存在一些局限性。因此，该细胞模型在广泛应用于脑内Aβ清除研究之前，尚需进一步的表征。© 2016 The Authors Journal of Neuroscience Research Published by Wiley Periodicals，Inc.
Alzheimer's disease and cerebral amyloid angiopathy are characterized by accumulation of amyloid‐β (Aβ) at the cerebrovasculature due to decreased clearance at the blood‐brain barrier (BBB). However, the exact mechanism of Aβ clearance across this barrier has not been fully elucidated. The hCMEC/D3 cell line has been characterized as a valid model for the BBB. In this study we evaluated the use of this model to study Aβ clearance across the BBB, with an emphasis on brain‐to‐blood directional permeability. Barrier integrity of hCMEC/D3 monolayers was confirmed for large molecules in both the apical to basolateral and the reverse direction. However, permeability for smaller molecules was substantially higher, especially in basolateral to apical direction, and barrier formation for Aβ was completely absent in this direction. In addition, hCMEC/D3 cells failed to develop a high TEER, possibly caused by incomplete formation of tight junctions. We conclude that the hCMEC/D3 model has several limitations to study the cerebral clearance of Aβ. Therefore, the model needs further characterization before this cell system can be generally applied as a model to study cerebral Aβ clearance. © 2016 The Authors Journal of Neuroscience Research Published by Wiley Periodicals, Inc.