Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture

Giovanni Giuseppe Giobbe, Claire Crowley, Camilla Luni, Sara Campinoti, Moustafa Khedr, Kai Kretzschmar, Martina Maria De Santis, Elisa Zambaiti, Federica Michielin, Laween Meran, Qianjiang Hu, Gijs van Son, Luca Urbani, Anna Manfredi, Monica Giomo, Simon Eaton, Davide Cacchiarelli, Vivian S. W. Li, Hans Clevers, Paola Bonfanti, Nicola Elvassore () and Paolo De Coppi ()
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Giovanni Giuseppe Giobbe: University College London GOS Institute of Child Health
Claire Crowley: University College London GOS Institute of Child Health
Camilla Luni: ShanghaiTech University
Sara Campinoti: University College London GOS Institute of Child Health
Moustafa Khedr: University College London GOS Institute of Child Health
Kai Kretzschmar: Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht
Martina Maria De Santis: University College London GOS Institute of Child Health
Elisa Zambaiti: University College London GOS Institute of Child Health
Federica Michielin: University College London GOS Institute of Child Health
Laween Meran: University College London GOS Institute of Child Health
Qianjiang Hu: ShanghaiTech University
Gijs van Son: Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht
Luca Urbani: University College London GOS Institute of Child Health
Anna Manfredi: Telethon Institute of Genetics and Medicine (TIGEM)
Monica Giomo: University of Padova
Simon Eaton: University College London GOS Institute of Child Health
Davide Cacchiarelli: Telethon Institute of Genetics and Medicine (TIGEM)
Vivian S. W. Li: the Francis Crick Institute
Hans Clevers: Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht
Paola Bonfanti: University College London GOS Institute of Child Health
Nicola Elvassore: University College London GOS Institute of Child Health
Paolo De Coppi: University College London GOS Institute of Child Health

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-13605-4

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