具有类似活体细胞复杂性和功能的生物工程人结肠器官组织

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING
Olga Mitrofanova, Mikhail Nikolaev, Quan Xu, Nicolas Broguiere, Irineja Cubela, J. Gray Camp, Michael Bscheider, Matthias P. Lutolf
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引用次数: 0

摘要

有机体和芯片器官已成为体外模拟人类肠道生理和疾病的强大工具。虽然这些系统与人体生理相关,但往往缺乏模拟人体肠道粘膜所需的环境氛围、空间组织、细胞类型多样性和成熟度。为了生成与体内组织近似的模型,我们在此整合了类器官和芯片上器官技术,开发出一种先进的人体类器官模型,称为 "迷你结肠"。通过采用不对称的生长因子刺激,我们大大提高了组织的寿命,并复制了类似于体内增殖和分化细胞类型的多样性和模式化。小结肠中含有大量分泌粘液的上睑细胞,单细胞 RNA 测序显示出新出现的成熟和功能性结肠细胞,这标志着小结肠的成熟。这种方法可扩展到从小肠生成微组织,并加入更多的微环境成分。最后,我们的生物工程器官组织为系统研究人类肠道生理和病理提供了一个精确的平台,也为药物安全性评估提供了一个可靠的临床前模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Bioengineered human colon organoids with in vivo-like cellular complexity and function

Bioengineered human colon organoids with in vivo-like cellular complexity and function

Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease in vitro. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling in vivo tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called “mini-colons.” By employing an asymmetric stimulation with growth factors, we greatly enhanced tissue longevity and replicated in vivo-like diversity and patterning of proliferative and differentiated cell types. Mini-colons contain abundant mucus-producing goblet cells and, signifying mini-colon maturation, single-cell RNA sequencing reveals emerging mature and functional colonocytes. This methodology is expanded to generate microtissues from the small intestine and incorporate additional microenvironmental components. Finally, our bioengineered organoids provide a precise platform to systematically study human gut physiology and pathology, and a reliable preclinical model for drug safety assessment.

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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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