Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids.
Development of a primary human Small Intestine-on-a-Chip using biopsy-derived organoids.
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DOI：
10.1038/s41598-018-21201-7
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发表时间：
2018-02-13
影响因子：
4.6
通讯作者：
Ingber DE
中科院分区：
文献类型：
--
作者：
Kasendra M;Tovaglieri A;Sontheimer-Phelps A;Jalili-Firoozinezhad S;Bein A;Chalkiadaki A;Scholl W;Zhang C;Rickner H;Richmond CA;Li H;Breault DT;Ingber DE
在这里，我们描述了一种用于制造原代人小肠芯片（肠芯片）的方法，该芯片含有从肠活检的健康区域分离的上皮细胞。原代上皮细胞被扩增为3D类器官，解离并在微流体装置内的多孔膜上培养，其中人肠道微血管内皮细胞在流动和循环变形下在平行微通道中培养。在肠芯片中，上皮形成绒毛状突起，其由经历类似于肠类器官的多谱系分化的极化上皮细胞排列，然而，这些细胞将其顶端表面暴露于开放的管腔并与内皮接触。转录组学分析还表明，与用于创建芯片的十二指肠类器官相比，肠芯片在体内更接近地模拟整个人类十二指肠。由于可以连续收集流过肠芯片内腔的液体，因此可以使用液体样品的顺序分析来量化体外多天内的营养消化、粘液分泌和肠屏障功能的建立。因此，肠道芯片可能是一种有用的研究工具，用于正常肠道功能至关重要的应用，包括代谢，营养，感染和药物药代动力学以及个性化医疗的研究。
Here we describe a method for fabricating a primary human Small Intestine-on-a-Chip (Intestine Chip) containing epithelial cells isolated from healthy regions of intestinal biopsies. The primary epithelial cells are expanded as 3D organoids, dissociated, and cultured on a porous membrane within a microfluidic device with human intestinal microvascular endothelium cultured in a parallel microchannel under flow and cyclic deformation. In the Intestine Chip, the epithelium forms villi-like projections lined by polarized epithelial cells that undergo multi-lineage differentiation similar to that of intestinal organoids, however, these cells expose their apical surfaces to an open lumen and interface with endothelium. Transcriptomic analysis also indicates that the Intestine Chip more closely mimics whole human duodenum in vivo when compared to the duodenal organoids used to create the chips. Because fluids flowing through the lumen of the Intestine Chip can be collected continuously, sequential analysis of fluid samples can be used to quantify nutrient digestion, mucus secretion and establishment of intestinal barrier function over a period of multiple days in vitro. The Intestine Chip therefore may be useful as a research tool for applications where normal intestinal function is crucial, including studies of metabolism, nutrition, infection, and drug pharmacokinetics, as well as personalized medicine.
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影响因子：
6.1
作者：
Grosberg A;Alford PW;McCain ML;Parker KK
通讯作者：
Parker KK
影响因子：
5.8
作者：
Eichler, GS;Huang, S;Ingber, DE
通讯作者：
Ingber, DE
DOI：
10.1073/pnas.1305823110
发表时间：
2013-10-29
影响因子：
11.1
作者：
Piccolo, Stephen R.;Withers, Michelle R.;Johnson, W. Evan
通讯作者：
Johnson, W. Evan
影响因子：
1.6
作者：
Imura, Yuki;Asano, Yasuyuki;Yoshimura, Etsuro
通讯作者：
Yoshimura, Etsuro
影响因子：
2.9
作者：
Baudoin, Regis;Griscom, Laurent;Leclerc, Eric
通讯作者：
Leclerc, Eric