In Vitro Generation of Mouse Colon Crypts.
In Vitro Generation of Mouse Colon Crypts.
复制标题
小鼠结肠隐窝的体外生成。
DOI：
10.1021/acsbiomaterials.7b00368
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发表时间：
2017
影响因子：
5.8
通讯作者：
Allbritton,NancyL
中科院分区：
文献类型：
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作者：
Wang,Yuli;Gunasekara,DulanB;Attayek,PeterJ;Reed,MarkI;DiSalvo,Matthew;Nguyen,DanielL;Dutton,JohannaS;Lebhar,MichaelS;Bultman,ScottJ;Sims,ChristopherE;Magness,ScottT;Allbritton,NancyL
类器官培养对肠上皮的蛋白体外研究有重要影响；然而，在体内发现的精致的结构、腔内可达性和谱系划分尚未在类器官系统中重现。我们使用具有合适细胞外基质接触和硬度的微工程平台来生成自我更新的小鼠结肠上皮，该上皮复制了体内发现的关键建筑和生理功能，包括具有极化隐窝的表面。基底-管腔轴的化学梯度分化了干细胞/祖细胞，并促进了沿其体外隐窝轴的适当谱系分化，从而使组织具有隐窝干细胞生态位以及覆盖管腔表面的分化细胞层。这种结合了微工程支架、天然化学梯度和生物物理线索的新方法可以作为一种功能强大、生理相关的体外组织模型。
Organoid culture has had a significant impact onin vitrostudies of the intestinal epithelium; however, the exquisite architecture, luminal accessibility, and lineage compartmentalization foundin vivohas not been recapitulated in the organoid systems. We have used a microengineered platform with suitable extracellular matrix contacts and stiffness to generate a self-renewing mouse colonic epithelium that replicates key architectural and physiological functions foundin vivo, including a surface lined with polarized crypts. Chemical gradients applied to the basal–luminal axis compartmentalized the stem/progenitor cells and promoted appropriate lineage differentiation along thein vitrocrypt axis so that the tissue possessed a crypt stem cell niche as well as a layer of differentiated cells covering the luminal surface. This new approach combining microengineered scaffolds, native chemical gradients, and biophysical cues to control primary epitheliumex vivocan serve as a highly functional and physiologically relevantin vitrotissue model.