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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

A fully defined 3D matrix for ex vivo expansion of human colonic organoids from biopsy tissue

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Vis graf over relationer

Intestinal organoids have widespread research and biomedical applications, such as disease modeling, drug testing and regenerative medicine. However, the transition towards clinical use has in part been hampered by the dependency on animal tumor-derived basement membrane extracts (BMEs), which are poorly defined and ill-suited for regulatory approval due to their origin and batch-to-batch variability. In order to overcome these limitations, and to enable clinical translation, we tested the use of a fully defined hydrogel matrix, QGel CN99, to establish and expand intestinal organoids directly from human colonic biopsies. We achieved efficient de novo establishment, expansion and organoid maintenance, while also demonstrating sustained genetic stability. Additionally, we were able to preserve stemness and differentiation capacity, with transcriptomic profiles resembling normal colonic epithelium. All data proved comparable to organoids cultured in the BME-benchmark Matrigel. The application of a fully defined hydrogel, completely bypassing the use of BMEs, will drastically improve the reproducibility and scalability of organoid studies, but also advance translational applications in personalized medicine and stem cell-based regenerative therapies.

OriginalsprogEngelsk
TidsskriftBiomaterials
Vol/bind262
Sider (fra-til)120248
ISSN0142-9612
DOI
StatusUdgivet - dec. 2020

Bibliografisk note

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

ID: 62087711