Abstract：
Human induced pluripotent stem cell (hiPSC)-derived intestinal organoids are valuable tools for researching developmental biology and personalized therapies, but their closed topology and relative immature state limit applications. Here, we use organ-on-chip technology to develop a hiPSC-derived intestinal barrier with apical and basolateral access in a more physiological in vitro microenvironment. To replicate growth factor gradients along the crypt-villus axis, we locally expose the cells to expansion and differentiation media. In these conditions, intestinal epithelial cells self-organize into villus-like folds with physiological barrier integrity, and myofibroblasts and neurons emerge and form a subepithelial tissue in the bottom channel. The growth factor gradients efficiently balance dividing and mature cell types and induce an intestinal epithelial composition, including absorptive and secretory lineages, resembling the composition of the human small intestine. This well-characterized hiPSC-derived intestine-on-chip system can facilitate personalized studies on physiological processes and therapy development in the human small intestine.
摘要：
人类诱导多能干细胞（hiPSC）来源的肠道类器官是研究发育生物学和个性化治疗的有价值的工具，但是它们的封闭拓扑和相对不成熟的状态限制了应用。这里,我们使用芯片上器官技术在更生理的体外微环境中开发出具有顶端和基底外侧通路的hiPSC衍生肠屏障。为了沿着隐窝-绒毛轴复制生长因子梯度，我们将细胞局部暴露于扩增和分化培养基中。在这些条件下,肠上皮细胞自组织成具有生理屏障完整性的绒毛样褶皱，肌成纤维细胞和神经元在底部通道中出现并形成上皮下组织。生长因子梯度有效地平衡分裂和成熟细胞类型，并诱导肠上皮成分，包括吸收和分泌谱系，类似于人类小肠的成分。这种特征良好的hiPSC衍生的芯片肠系统可以促进对人类小肠中的生理过程和治疗开发的个性化研究。
