日本京都大学Kazuo Takayama研究团队的一项最新研究研制了通过再现间质流动构建多层小肠样组织。这一研究成果发表在2024年7月11日出版的国际学术期刊《细胞—干细胞》上。

该研究组发现，在胚胎器官发生过程中，肠道内由循环血浆提供动力的间质流动是一个至关重要的因素。该课题组研究人员的目标是通过将间质流整合到系统中，构建一个体内样的多层小肠组织，然后在能够再现间质流的微流控装置上同时从人类多能干细胞中，分化出最终的内胚层细胞和中胚层细胞，从而开发出微型小肠系统。

这种方法促进了细胞成熟，并导致三维小肠样组织的发育，具有绒毛样上皮和排列的间充质层。他们的微小肠系统不仅克服了传统肠道模型的局限性，而且为深入了解肠道组织发育的详细机制提供了独特的机会。

据悉，最近的进展使体外模拟人类小肠成为可能，但要全面概括其结构和功能特征仍然是一个挑战。

附：英文原文

Title: Construction of multilayered small intestine-like tissue by reproducing interstitial flow

Author: Sayaka Deguchi, Kaori Kosugi, Naoki Takeishi, Yukio Watanabe, Shiho Morimoto, Ryosuke Negoro, Fuki Yokoi, Hiroki Futatsusako, May Nakajima-Koyama, Mio Iwasaki, Takuya Yamamoto, Yoshiya Kawaguchi, Yu-suke Torisawa, Kazuo Takayama

Issue&Volume: 2024-07-11

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.

DOI: 10.1016/j.stem.2024.06.012

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00220-0