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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月28日

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

摘要

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.