In vitro differentiation of human intestinal organoids (HIOs) from pluripotent stem cells is an unparalleled system for creating complex, multicellular three-dimensional structures capable of giving rise to tissue analogous to native human tissue. Current methods for generating HIOs rely on growth in an undefined tumour-derived extracellular matrix (ECM), which severely limits the use of organoid technologies for regenerative and translational medicine. Here, we developed a fully defined, synthetic hydrogel based on a four-armed, maleimide-terminated poly(ethylene glycol) macromer that supports robust and highly reproducible in vitro growth and expansion of HIOs, such that three-dimensional structures are never embedded in tumour-derived ECM. We also demonstrate that the hydrogel serves as an injection vehicle that can be delivered into injured intestinal mucosa resulting in HIO engraftment and improved colonic wound repair. Together, these studies show proof-of-concept that HIOs may be used therapeutically to treat intestinal injury.

中文翻译：

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用于人体肠道类器官生成和结肠伤口修复的合成水凝胶。

人类肠道类器官 (HIO) 从多能干细胞的体外分化是一个无与伦比的系统，用于创建复杂的多细胞三维结构，能够产生类似于天然人体组织的组织。目前产生 HIO 的方法依赖于不确定的肿瘤衍生细胞外基质 (ECM) 的生长，这严重限制了类器官技术在再生医学和转化医学中的应用。在这里，我们开发了一种基于四臂、马来酰亚胺封端的聚（乙二醇）大分子单体的完全定义的合成水凝胶，该大分子单体支持 HIO 的稳健且高度可重复的体外生长和扩展，因此三维结构永远不会嵌入肿瘤来源的 ECM。我们还证明水凝胶可作为注射载体，可以输送到受伤的肠粘膜中，从而导致 HIO 植入并改善结肠伤口修复。总之，这些研究表明 HIOs 可用于治疗肠道损伤的概念验证。