Mechano-modulatory synthetic niches for liver organoid derivation
Mechano-modulatory synthetic niches for liver organoid derivation
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 modeling1–5. 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 applications6. We here used chemically defined hydrogels for the efficient derivation of both mouse and human hepatic organoids. Organoid growth was found to be highly stiffness-sensitive and dependent on yes-associated protein 1 (YAP) activity. However, in contrast to intestinal organoids7, YAP-mediated stiffness sensitivity was independent of acto-myosin contractility, requiring instead activation of the Src family of kinases (SFKs). Aberrant matrix stiffness on the other hand led to a shift in the progenitor phenotype, resulting in compromised proliferative capacity. Finally, we demonstrate the unprecedented 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.
Rezakhani Saba、Yildiz Ece、Nuciforo Sandro、Heim Markus H.、Schoonjans Kristina、Sorrentino Giovanni、Lutolf Matthias P.
Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, ¨|cole Polytechnique F¨|d¨|rale de Lausanne (EPFL)Laboratory of Metabolic Signaling, Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique F¨|d¨|rale de LausanneDepartment of Biomedicine, University Hospital Basel, University of BaselDepartment of Biomedicine, University Hospital Basel, University of Basel||Clinic of Gastroenterology and Hepatology, University Hospital Basel, University of BaselLaboratory of Metabolic Signaling, Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique F¨|d¨|rale de LausanneLaboratory of Metabolic Signaling, Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique F¨|d¨|rale de LausanneLaboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, ¨|cole Polytechnique F¨|d¨|rale de Lausanne (EPFL)
基础医学生物科学研究方法、生物科学研究技术生物工程学
Rezakhani Saba,Yildiz Ece,Nuciforo Sandro,Heim Markus H.,Schoonjans Kristina,Sorrentino Giovanni,Lutolf Matthias P..Mechano-modulatory synthetic niches for liver organoid derivation[EB/OL].(2025-03-28)[2025-04-24].https://www.biorxiv.org/content/10.1101/810275.点此复制
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