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

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING
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
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引用次数: 0

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.

Abstract Image

通过再现间隙流构建多层小肠样组织
最近的研究进展使体外模拟人类小肠成为可能,但要完全再现其结构和功能特征仍是一项挑战。我们怀疑胚胎器官形成过程中由循环血浆驱动的肠道内间隙流动是一个重要因素。我们的目标是通过在系统中加入间隙流来构建类似活体的多层小肠组织,进而通过在能够复制间隙流的微流体装置上同时分化人类多能干细胞的确定性内胚层和中胚层细胞来开发微型小肠系统。这种方法提高了细胞的成熟度,并培育出了具有绒毛状上皮和排列整齐的间质层的三维小肠样组织。我们的微型小肠系统不仅克服了传统肠道模型的局限性,还为深入了解肠道组织发育的详细机制提供了一个独特的机会。
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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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