Human intestinal spheroids cultured using Sacrificial Micromolding as a model system for studying drug transport.
Human intestinal spheroids cultured using Sacrificial Micromolding as a model system for studying drug transport.
复制标题
使用牺牲微成型培养的人类肠道球体作为研究药物转运的模型系统。
DOI：
10.1038/s41598-019-46408-0
复制
发表时间：
2019
影响因子：
4.6
通讯作者：
Desai,TejalA
中科院分区：
文献类型：
--
作者：
Samy,KarenE;Levy,ElizabethS;Phong,Kiet;Demaree,Benjamin;Abate,AdamR;Desai,TejalA
In vitromodels of the small intestine are crucial tools for the prediction of drug absorption. The Caco-2 monolayer transwell model has been widely employed to assess drug absorption across the intestine. However, it is now well-established that 3Din vitromodels capture tissue-specific architecture and interactions with the extracellular matrix and therefore better recapitulate the complexin vivoenvironment. However, these models need to be characterized for barrier properties and changes in gene expression and transporter function. Here, we report that geometrically controlled self-assembling multicellular intestinal Caco-2 spheroids cultured using Sacrificial Micromolding display reproducible intestinal features and functions that are more representative of thein vivosmall intestine than the widely used 2D transwell model. We show that Caco-2 cell maturation and differentiation into the intestinal epithelial phenotype occur faster in spheroids and that they are viable for a longer period of time. Finally, we were able to invert the polarity of the spheroids by culturing them around Matrigel beads allowing superficial access to the apical membrane and making the model more physiological. This robust and reproduciblein vitrointestinal model could serve as a valuable system to expedite drug screening as well as to study intestinal transporter function.
