TY - JOUR KW - Biotechnology KW - medical research AU - Wim B. M. de Lau AU - Joost J. A. P. M. Wijnakker AU - Gijs J. F. van Son AU - Daniel Krueger AU - Daisong Wang AU - Matthijs S. Abendroth AU - Robin Schreurs AU - Claudia Y. Janda AU - Fenna L. H. van Rijt AU - Benjamin J. P. Chalopin AU - Emma Bokobza AU - Johan H. van Es AU - Timothy A. Springer AU - Arnoud Sonnenberg AU - Hans Clevers AB - 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. BT - Nature Biotechnology DA - 2025-10-28 DO - 10.1038/s41587-025-02874-8 LA - en N2 - 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. PY - 2025 SP - 1 EP - 11 T2 - Nature Biotechnology TI - A single-chain derivative of an integrin-activating antibody potentiates organoid growth in Matrigel and collagen hydrogels UR - https://www.nature.com/articles/s41587-025-02874-8 Y2 - 2025-12-02 SN - 1546-1696 ER -