Laboratory of Metabolic Signaling, Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland.
Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences and School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
Nat Commun. 2020 Jul 10;11(1):3416. doi: 10.1038/s41467-020-17161-0.
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.
最近的研究表明，从肝脏中分离的原代细胞可以在体外作为类器官扩增，这为再生医学和疾病建模带来了巨大的希望。然而，基于定义不明确且可能具有免疫原性的基质的三维（3D）培养物的使用，阻碍了肝类器官技术向实际应用的转化。我们在这里使用化学定义的水凝胶来有效地衍生小鼠和人类的肝类器官。研究发现，类器官的生长对刚度非常敏感，这种机制独立于肌动球蛋白收缩性，而需要激活Src 家族激酶（SFKs）和 yes 相关蛋白 1（YAP）。另一方面，基质刚度异常会导致增殖能力受损。最后，我们证明了在不使用动物成分的情况下，从活检中建立人类肝脏类器官，并且在整个过程中都不需要使用动物成分。因此，我们的方法为建立基于肝类器官的再生医学的方案开辟了令人兴奋的前景。
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