Reconstructing the Human Renal Vascular-Tubular Unit In Vitro.
Reconstructing the Human Renal Vascular-Tubular Unit In Vitro.
复制标题
在体外重建人肾血管管单元。
DOI：
10.1002/adhm.201801120
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发表时间：
2018-12
影响因子：
10
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Rayner SG;Phong KT;Xue J;Lih D;Shankland SJ;Kelly EJ;Himmelfarb J;Zheng Y
经过工程设计的人类单芯片肾脏平台在疾病建模和药物筛选方面显示出巨大的前景。然而，在重建复杂的结构、细胞组成和基质组成方面存在着突出的挑战，这是正确模拟肾功能所必需的。在这里，我们报告了第一个完全可调的人类芯片上肾平台，该平台允许使用完全细胞可重构的基质和患者来源的肾脏细胞重建肾内皮细胞-上皮交换界面的自然架构。该平台由双层人肾血管-肾小管单位(HRVTU)组成，由一层薄的胶原膜复制肾脏交换界面。我们发现，衬里各自管腔的内皮细胞和上皮细胞将培养中的膜重塑为大约1微米厚的交换界面，由天然基底膜蛋白组成。该界面为介质流动和血液灌流显示了足够的机械完整性。作为原理证明，我们的hRVTU执行肾脏特有的功能，包括从上皮通道重吸收白蛋白和葡萄糖。通过合并来自单一捐赠者的多个细胞群体，我们证明了我们的hRVTU可能在未来的精确医学应用中具有实用价值。我们系统的成功为下一代芯片上器官模型提供了新的机会。
Engineered human kidney-on-a-chip platforms show tremendous promise for disease modeling and drug screening. Outstanding challenges exist, however, in reconstructing the complex architecture, cellular make-up, and matrix composition necessary for the proper modeling of kidney function. Here, we report the first fully tunable human kidney-on-a-chip platform that allows the reconstruction of the native architecture of the renal endothelial-epithelial exchange interface using entirely cell-remodelable matrix and patient-derived kidney cells. This platform consists of a double-layer human renal vascular-tubular unit (hRVTU) enabled by a thin collagen membrane that replicates the kidney exchange interface. We show that endothelial and epithelial cells lining their respective lumens remodel the membrane in culture into an approximately 1 µm-thick exchange interface composed of native basement membrane proteins. This interface displays sufficient mechanical integrity for media flow and blood perfusion. As a proof of principle, we demonstrate that our hRVTU performs kidney-specific functions including reabsorption of albumin and glucose from the epithelial channel. By incorporating multiple cell populations from single donors, we demonstrate that our hRVTU may have utility for future precision medicine applications. The success of our system provides new opportunities for the next generation of organ-on-a-chip models.
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影响因子：
3.8
作者：
Ferrell, Nicholas;Ricci, Kevin B.;Groszek, Joseph;Marmerstein, Joseph T.;Fissell, William H.
通讯作者：
Fissell, William H.
影响因子：
4.6
作者：
Jansen J;Fedecostante M;Wilmer MJ;Peters JG;Kreuser UM;van den Broek PH;Mensink RA;Boltje TJ;Stamatialis D;Wetzels JF;van den Heuvel LP;Hoenderop JG;Masereeuw R
通讯作者：
Masereeuw R
影响因子：
13.6
作者：
Ligresti, Giovanni;Nagao, Ryan J.;Zheng, Ying
通讯作者：
Zheng, Ying
影响因子：
46.9
作者：
Bhatia, Sangeeta N.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
影响因子：
6.1
作者：
Jang, Kyung-Jin;Suh, Kahp-Yang
通讯作者：
Suh, Kahp-Yang