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Growth of Epithelial Organoids in a Defined Hydrogel. | LitMetric

AI Article Synopsis

  • Epithelial organoids are lab-grown miniaturized organs from stem cells, used for studying organ development and diseases, as well as drug testing.
  • Current methods depend on animal-derived materials for support, which limits regeneration potential, prompting research into better scaffolding solutions.
  • It was discovered that soft fibrin-based hydrogels, combined with specific adhesion molecules, allow for stable organoid growth and long-term maintenance, offering a more versatile alternative to traditional scaffolds.

Article Abstract

Epithelial organoids are simplified models of organs grown in vitro from embryonic and adult stem cells. They are widely used to study organ development and disease, and enable drug screening in patient-derived primary tissues. Current protocols, however, rely on animal- and tumor-derived basement membrane extract (BME) as a 3D scaffold, which limits possible applications in regenerative medicine. This prompted us to study how organoids interact with their matrix, and to develop a well-defined hydrogel that supports organoid generation and growth. It is found that soft fibrin matrices provide suitable physical support, and that naturally occurring Arg-Gly-Asp (RGD) adhesion domains on the scaffold, as well as supplementation with laminin-111, are key parameters required for robust organoid formation and expansion. The possibility to functionalize fibrin via factor XIII-mediated anchoring also allows to covalently link fluorescent nanoparticles to the matrix for 3D traction force microscopy. These measurements suggest that the morphogenesis of budding intestinal organoids results from internal pressure combined with higher cell contractility in the regions containing differentiated cells compared to the regions containing stem cells. Since the fibrin/laminin matrix supports long-term expansion of all tested murine and human epithelial organoids, this hydrogel can be widely used as a defined equivalent to BME.

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Source
http://dx.doi.org/10.1002/adma.201801621DOI Listing

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