Mechano-modulatory synthetic niches for liver organoid derivation

Giovanni Sorrentino, Saba Rezakhani, Ece Yildiz, Sandro Nuciforo, Markus H. Heim, Matthias P. Lutolf () and Kristina Schoonjans ()
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Giovanni Sorrentino: Ecole Polytechnique Fédérale de Lausanne
Saba Rezakhani: École Polytechnique Fédérale de Lausanne (EPFL)
Ece Yildiz: Ecole Polytechnique Fédérale de Lausanne
Sandro Nuciforo: University Hospital Basel, University of Basel
Markus H. Heim: University Hospital Basel, University of Basel
Matthias P. Lutolf: École Polytechnique Fédérale de Lausanne (EPFL)
Kristina Schoonjans: Ecole Polytechnique Fédérale de Lausanne

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract The recent demonstration that primary cells from the liver can be expanded in vitro as organoids holds enormous promise for regenerative medicine and disease modelling. The use of three-dimensional (3D) cultures based on ill-defined and potentially immunogenic matrices, however, hampers the translation of liver organoid technology into real-life applications. We here use chemically defined hydrogels for the efficient derivation of both mouse and human hepatic organoids. Organoid growth is found to be highly stiffness-sensitive, a mechanism independent of acto-myosin contractility and requiring instead activation of the Src family of kinases (SFKs) and yes-associated protein 1 (YAP). Aberrant matrix stiffness, on the other hand, results in compromised proliferative capacity. Finally, we demonstrate the establishment of biopsy-derived human liver organoids without the use of animal components at any step of the process. Our approach thus opens up exciting perspectives for the establishment of protocols for liver organoid-based regenerative medicine.

Date: 2020
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DOI: 10.1038/s41467-020-17161-0

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