Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture

• Published in: Nature communications Vol. 10; no. 1; pp. 5658 - 14
• Main Authors: Giobbe, Giovanni Giuseppe, Crowley, Claire, Luni, Camilla, Campinoti, Sara, Khedr, Moustafa, Kretzschmar, Kai, De Santis, Martina Maria, Zambaiti, Elisa, Michielin, Federica, Meran, Laween, Hu, Qianjiang, van Son, Gijs, Urbani, Luca, Manfredi, Anna, Giomo, Monica, Eaton, Simon, Cacchiarelli, Davide, Li, Vivian S. W., Clevers, Hans, Bonfanti, Paola, Elvassore, Nicola, De Coppi, Paolo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.12.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 14/1; 14/19; 14/35; 14/63; 147/135; 38/77; 38/90; 38/91; 59; 631/532/2118/2437; 631/532/2437; 631/61/54/994; 631/80/79/750; 64; 64/60; 82/58; Animals; Cell culture; Cell growth; Cell Proliferation; Derivation; Endoderm; Endoderm - growth & development; Endoderm - metabolism; Extracellular matrix; Extracellular Matrix - chemistry; Extracellular Matrix - metabolism; Gels; Humanities and Social Sciences; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - metabolism; Intestine; Medicine; multidisciplinary; Organoids; Organoids - growth & development; Organoids - metabolism; Pancreas; Regenerative medicine; Science; Science (multidisciplinary); Small intestine; Swine; System effectiveness; Tissue engineering; Tissue Engineering - instrumentation; Tissue Scaffolds - chemistry; Tissues; Transcriptomics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13605-4

Organoids have extensive therapeutic potential and are increasingly opening up new avenues within regenerative medicine. However, their clinical application is greatly limited by the lack of effective GMP-compliant systems for organoid expansion in culture. Here, we envisage that the use of extracellular matrix (ECM) hydrogels derived from decellularized tissues (DT) can provide an environment capable of directing cell growth. These gels possess the biochemical signature of tissue-specific ECM and have the potential for clinical translation. Gels from decellularized porcine small intestine (SI) mucosa/submucosa enable formation and growth of endoderm-derived human organoids, such as gastric, hepatic, pancreatic, and SI. ECM gels can be used as a tool for direct human organoid derivation, for cell growth with a stable transcriptomic signature, and for in vivo organoid delivery. The development of these ECM-derived hydrogels opens up the potential for human organoids to be used clinically. Organoid cultures have been developed from multiple tissues, opening new possibilities for regenerative medicine. Here the authors demonstrate the derivation of GMP-compliant hydrogels from decellularized porcine small intestine which support formation and growth of human gastric, liver, pancreatic and small intestinal organoids.