瑞士人类生物学研究所Matthias P. Lutolf研究组近日取得一项新成果。经过不懈努力，他们开发了具有体内样细胞复杂性和功能的生物工程人类结肠类器官。相关论文发表在2024年6月13日出版的《细胞—干细胞》杂志上。

为了生成与体内组织非常相似的模型，该课题组在此整合了类器官和器官芯片技术，开发了一种先进的人类类器官模型，称为“迷你结肠”。通过使用生长因子的不对称刺激，该课题组大大提高了组织寿命，并复制了体内样的多样性和增殖和分化细胞类型的模式。迷你结肠含有丰富的产生黏液的杯状细胞，单细胞RNA测序显示了迷你结肠的成熟和功能。

这种方法被扩展到从小肠产生微组织，并包含额外的微环境成分。最后，他们的生物工程类器官为系统研究人类肠道生理和病理提供了精确的平台，并为药物安全性评估提供了可靠的临床前模型。

研究人员表示，类器官和器官芯片已成为模拟人体肠道生理和疾病的强大工具，尽管这些系统具有生理相关性，但它们通常缺乏模拟人类肠粘膜所需的环境介质、空间组织、细胞类型多样性和成熟度。

附：英文原文

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

Author: Olga Mitrofanova, Mikhail Nikolaev, Quan Xu, Nicolas Broguiere, Irineja Cubela, J. Gray Camp, Michael Bscheider, Matthias P. Lutolf

Issue&Volume: 2024-06-13

Abstract: 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.

DOI: 10.1016/j.stem.2024.05.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(24)00184-X