TY - JOUR
T1 - A single-chain derivative of an integrin-activating antibody potentiates organoid growth in Matrigel and collagen hydrogels
AU - de Lau, Wim B.M.
AU - Wijnakker, Joost J.A.P.M.
AU - van Son, Gijs J.F.
AU - Krueger, Daniel
AU - Wang, Daisong
AU - Abendroth, Matthijs S.
AU - Schreurs, Robin
AU - Janda, Claudia Y.
AU - van Rijt, Fenna L.H.
AU - Chalopin, Benjamin J.P.
AU - Bokobza, Emma
AU - van Es, Johan H.
AU - Springer, Timothy A.
AU - Sonnenberg, Arnoud
AU - Clevers, Hans
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025
Y1 - 2025
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.
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.
UR - https://www.scopus.com/pages/publications/105019923488
UR - https://www.mendeley.com/catalogue/d684e6ee-4590-3459-9a2e-1bdefa507429/
U2 - 10.1038/s41587-025-02874-8
DO - 10.1038/s41587-025-02874-8
M3 - Article
AN - SCOPUS:105019923488
SN - 1087-0156
JO - Nature biotechnology
JF - Nature biotechnology
ER -