Abstract:
Recent advances have made modeling human small intestines in vitro possible, but it remains a challenge to recapitulate fully their structural and functional characteristics. We suspected interstitial flow within the intestine, powered by circulating blood plasma during embryonic organogenesis, to be a vital factor. We aimed to construct an in vivo-like multilayered small intestinal tissue by incorporating interstitial flow into the system and, in turn, developed the micro-small intestine system by differentiating definitive endoderm and mesoderm cells from human pluripotent stem cells simultaneously on a microfluidic device capable of replicating interstitial flow. This approach enhanced cell maturation and led to the development of a three-dimensional small intestine-like tissue with villi-like epithelium and an aligned mesenchymal layer. Our micro-small intestine system not only overcomes the limitations of conventional intestine models but also offers a unique opportunity to gain insights into the detailed mechanisms underlying intestinal tissue development.
摘要:
最近的进展使体外模拟人类小肠成为可能,但要完全概括它们的结构和功能特征仍然是一个挑战。我们怀疑肠道内的间质流,在胚胎器官发生过程中由循环血浆提供动力,成为一个重要因素。我们旨在通过将间质流纳入系统来构建体内多层小肠组织,反过来,通过在能够复制间质流的微流体装置上同时区分定形内胚层和中胚层细胞与人多能干细胞,开发了小肠系统。这种方法增强了细胞成熟,并导致了具有绒毛样上皮和对齐的间充质层的三维小肠样组织的发育。我们的小肠系统不仅克服了传统肠道模型的局限性,而且还提供了一个独特的机会来深入了解肠道组织发育的详细机制。