In vitro Studies of Transendothelial Migration for Biological and Drug Discovery.
In vitro Studies of Transendothelial Migration for Biological and Drug Discovery.
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DOI：
10.3389/fmedt.2020.600616
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发表时间：
2020
影响因子：
--
通讯作者：
McGrath JL
中科院分区：
文献类型：
--
作者：
Salminen AT;Allahyari Z;Gholizadeh S;McCloskey MC;Ajalik R;Cottle RN;Gaborski TR;McGrath JL
炎症性疾病和癌症转移缺乏具体的药物来有效治疗，尽管我们对疾病进展的理解有了很大的进步。在生物学和药学上仍有待充分探索的这些疾病发病机制的一个特征是癌症和免疫细胞在外渗过程中从血液到下层组织的通道。无论迁移细胞类型如何，外渗的所有步骤都涉及分子相互作用，这些分子相互作用作为药物抑制或促进的靶点的丰富景观。跨内皮迁移（TEM）或细胞通过血管内皮的迁移是一个特别有前途的领域，因为它构成了外渗级联中最后和最重要的步骤。虽然癌症转移和炎性疾病的体内模型有助于我们目前对TEM的理解，但如果不使用体外平台，则会严重缺乏围绕这种现象的知识。除了易于使用、低成本和高可控性之外，体外平台允许使用人细胞系来更好地代表疾病病理学的某些特征，如在临床中所见。这些优于传统临床前模型的功效和毒性测试的益处在现代追求新型候选药物中尤其重要。在这里，我们回顾了白细胞和癌细胞外渗所涉及的细胞和分子事件，重点关注TEM，正如体外平台所发现的那样。特别是TEM的体外研究，展示了在实验室工作台上取得的巨大实验进展，并突出了体外生物发现平台的历史成功。这一成功显示了将这些平台应用于药物化合物筛选的潜力。除了免疫和癌细胞TEM，我们还讨论了肝细胞移植的前景，在这个过程中，全身性输送的肝细胞必须穿过肝窦内皮细胞才能成功移植并恢复肝功能。最后，简要总结了透射电镜研究中多孔膜的发展方向。
Inflammatory diseases and cancer metastases lack concrete pharmaceuticals for their effective treatment despite great strides in advancing our understanding of disease progression. One feature of these disease pathogeneses that remains to be fully explored, both biologically and pharmaceutically, is the passage of cancer and immune cells from the blood to the underlying tissue in the process of extravasation. Regardless of migratory cell type, all steps in extravasation involve molecular interactions that serve as a rich landscape of targets for pharmaceutical inhibition or promotion. Transendothelial migration (TEM), or the migration of the cell through the vascular endothelium, is a particularly promising area of interest as it constitutes the final and most involved step in the extravasation cascade. While in vivo models of cancer metastasis and inflammatory diseases have contributed to our current understanding of TEM, the knowledge surrounding this phenomenon would be significantly lacking without the use of in vitro platforms. In addition to the ease of use, low cost, and high controllability, in vitro platforms permit the use of human cell lines to represent certain features of disease pathology better, as seen in the clinic. These benefits over traditional pre-clinical models for efficacy and toxicity testing are especially important in the modern pursuit of novel drug candidates. Here, we review the cellular and molecular events involved in leukocyte and cancer cell extravasation, with a keen focus on TEM, as discovered by seminal and progressive in vitro platforms. In vitro studies of TEM, specifically, showcase the great experimental progress at the lab bench and highlight the historical success of in vitro platforms for biological discovery. This success shows the potential for applying these platforms for pharmaceutical compound screening. In addition to immune and cancer cell TEM, we discuss the promise of hepatocyte transplantation, a process in which systemically delivered hepatocytes must transmigrate across the liver sinusoidal endothelium to successfully engraft and restore liver function. Lastly, we concisely summarize the evolving field of porous membranes for the study of TEM.
影响因子：
8.8
作者：
Price, EA;Coombe, DR;Murray, JC
通讯作者：
Murray, JC