02058nas a2200337   4500000000100000000000100001008004100002260001500043653001800058653002100076100002100097700003200118700002300150700001900173700001700192700002600209700001900235700002100254700002500275700002800300700001700328700002000345700002400365700002200389700001700411245012800428856005500556300000900611520108600620022001401706       2025                            d  c2025-10-2810aBiotechnology10amedical research1 aWim B. M. de Lau1 aJoost J. A. P. M. Wijnakker1 aGijs J. F. van Son1 aDaniel Krueger1 aDaisong Wang1 aMatthijs S. Abendroth1 aRobin Schreurs1 aClaudia Y. Janda1 aFenna L. H. van Rijt1 aBenjamin J. P. Chalopin1 aEmma Bokobza1 aJohan H. van Es1 aTimothy A. Springer1 aArnoud Sonnenberg1 aHans Clevers00aA single-chain derivative of an integrin-activating antibody potentiates organoid growth in Matrigel and collagen hydrogels  uhttps://www.nature.com/articles/s41587-025-02874-8  a1-113 aCurrent 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.  a1546-1696