荷兰皇家艺术与科学学院Hans Clevers团队近日取得一项新成果。经过不懈努力，他们提出了整合素激活抗体的单链衍生物增强了基质凝胶和胶原蛋白水凝胶中的类器官生长。这一研究成果发表在2025年10月28日出版的国际学术期刊《自然—生物技术》上。

在这里，研究团队描述了一种单链（sc）版本的抗体TS2/16，它在类器官中变构激活整合素β1的功能。将单体scTS2/16添加到类器官培养基中，在Matrigel中生长的所有胃肠道类器官的产量增加了5倍。

此外，scTS2/16支持在胶原I水凝胶中培养时，这些类器官的产量增加6到7倍，无论是3D还是2D。I型胶原定义明确，可用于临床级制剂，当与scTS2/16联合使用时，可能支持来自胃肠道组织和其他上皮组织的上皮类器官的临床应用。

据了解，目前从成人干细胞中培养人类上皮类器官的方法可能与临床应用不兼容，因为它们依赖于异种、化学上未定义或非标准化的成分，如基底膜提取物Matrigel。Matrigel提供细胞外基质分子，包括层粘连蛋白和胶原IV，它们与类器官细胞上表达的β1整合素相互作用。

附：英文原文

Title: A single-chain derivative of an integrin-activating antibody potentiates organoid growth in Matrigel and collagen hydrogels

Author: de Lau, Wim B. M., Wijnakker, Joost J. A. P. M., van Son, Gijs J. F., Krueger, Daniel, Wang, Daisong, Abendroth, Matthijs S., Schreurs, Robin, Janda, Claudia Y., van Rijt, Fenna L. H., Chalopin, Benjamin J. P., Bokobza, Emma, van Es, Johan H., Springer, Timothy A., Sonnenberg, Arnoud, Clevers, Hans

Issue&Volume: 2025-10-28

Abstract: Current methods of culturing human epithelial organoids from adult stem cells may not be compatible with clinical applications as they rely on xenogeneic, chemically undefined or non-standardized components such as the basement membrane extract Matrigel. Matrigel provides a source of extracellular matrix molecules, including laminins and collagen IV, which interact with β1 integrins expressed on organoid cells. Here we describe a single-chain (sc) version of antibody TS2/16 that allosterically activates integrin β1 function in organoids. The addition of monomeric scTS2/16 to organoid medium results in up to a fivefold increase in the yield of all gastrointestinal organoids grown in Matrigel. Moreover, scTS2/16 supports a six- to sevenfold increase in the yield of these organoids when cultured in collagen I hydrogels, both in 3D and 2D. Collagen I is well defined, available in clinical-grade formulations and, when combined with scTS2/16, may support the clinical application of epithelial organoids derived from gastrointestinal tissues and other epithelial sources.

DOI: 10.1038/s41587-025-02874-8

Source: https://www.nature.com/articles/s41587-025-02874-8