Air-Liquid interface cultures to model drug delivery through the mucociliary epithelial barrier.

Air-Liquid interface cultures to model drug delivery through the mucociliary epithelial barrier.
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DOI:
10.1016/j.addr.2023.114866
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发表时间:
2023-07-01
影响因子:
16.1
通讯作者:
Randell, Scott H
Randell, Scott H
中科院分区:
医学1区
文献类型:
--
作者:
Lee, Rhianna E;Reidel, Boris;Randell, Scott H

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来自气道粘膜纤毛部分的上皮细胞可以很容易地在体外生长和扩增。当生长在气液界面(ALI)的多孔膜上时,细胞形成了一个融合的、电阻性的屏障,将顶端和基底外侧分隔开。ALI培养复制了体内上皮的关键形态、分子和功能特征,包括粘液分泌和粘液纤毛运输。根尖分泌物含有分泌的凝胶形成粘蛋白,脱落细胞相关的栓系粘蛋白,以及数百个参与宿主防御和体内平衡的额外分子。呼吸道上皮细胞ALI模型是一种经过时间验证的工具,已被用于阐明纤毛粘膜装置的结构和功能以及疾病发病机制的各种研究。它可以作为针对气道疾病的小分子和基因治疗的关键里程碑测试。为了充分利用这个重要工具的潜力,必须仔细考虑并仔细执行许多技术变量。
Epithelial cells from mucociliary portions of the airways can be readily grown and expanded in vitro. When grown on a porous membrane at an air-liquid interface (ALI) the cells form a confluent, electrically resistive barrier separating the apical and basolateral compartments. ALI cultures replicate key morphological, molecular and functional features of the in vivo epithelium, including mucus secretion and mucociliary transport. Apical secretions contain secreted gel-forming mucins, shed cell-associated tethered mucins, and hundreds of additional molecules involved in host defense and homeostasis. The respiratory epithelial cell ALI model is a time-proven workhorse that has been employed in various studies elucidating the structure and function of the mucociliary apparatus and disease pathogenesis. It serves as a critical milestone test for small molecule and genetic therapies targeting airway diseases. To fully exploit the potential of this important tool, numerous technical variables must be thoughtfully considered and carefully executed.