Giovanni Giuseppe Giobbe; Claire Crowley; Camilla Luni; Sara Campinoti; Moustafa Khedr; Kai Kretzschmar; Martina M. De Santis; Elisa Zambaiti; Federica Michielin; Laween Meran; Qianjiang Hu; Gijs J. F. van Son; Luca Urbani; Manfredi Anna; Monica Giomo; Simon Eaton; Davide Cacchiarelli; Vivian Li; Hans Clevers; Paola Bonfanti; Nicola Elvassore; Paolo De Coppi · 2019 · Nature Communications
Paper
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.
Analysis
This paper presents decellularized tissue-derived extracellular matrix (ECM) hydrogels as a GMP-compliant system for expanding endodermal organoids, overcoming a major limitation for clinical applications.
Discovery
Hanyu H; Sugimoto S; Sato T
Gulino ME; Mahida YR
Martinez-Espuga M; Mata A; Ordóñez-Morán P
Zhou H; Okkelman IA; De Kinder A; Devriendt B; Nobis M; Dmitriev RI
Wijnakker JJAPM; Clevers H
Haochen Yang; Byung Ho Lee; Anne Grapin-Botton; Heather A. Harrington; Helen M. Byrne
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