Vrije Universiteit Brussel, Liver Cell Biology Laboratory, Faculty of Medicine & Pharmacy, Basic Biomedical Sciences, Laarbeeklaan 103, 1090 Brussels, Belgium.
Adv Drug Deliv Rev. 2017 Nov 1;121:133-146. doi: 10.1016/j.addr.2017.07.004. Epub 2017 Jul 8.
Animal testing is still the most popular preclinical assessment model for liver fibrosis. To develop efficient anti-fibrotic therapies, robust and representative in vitro models are urgently needed. The most widely used in vitro fibrosis model is the culture-induced activation of primary rodent hepatic stellate cells. While these cultures have contributed greatly to the current understanding of hepatic stellate cell activation, they seem to be inadequate to cover the complexity of this regenerative response. This review summarizes recent progress towards the development of 3D culture models of liver fibrosis. Thus far, only a few hepatic culture systems have successfully implemented hepatic stellate cells (or other non-parenchymal cells) into hepatocyte cultures. Recent advances in bioprinting, spheroid- and precision-cut liver slice cultures and the use of microfluidic bioreactors will surely lead to valid 3D in vitro models of liver fibrosis in the near future.
动物试验仍然是肝纤维化的最流行的临床前评估模型。为了开发有效的抗纤维化疗法，迫切需要稳健且具有代表性的体外模型。最广泛使用的体外纤维化模型是原代啮齿动物肝星状细胞的培养诱导激活。虽然这些培养物极大地促进了对肝星状细胞激活的当前理解，但它们似乎不足以涵盖这种再生反应的复杂性。本文综述了肝纤维化三维培养模型的最新进展。迄今为止，只有少数肝培养系统成功地将肝星状细胞（或其他非实质细胞）纳入肝细胞培养中。生物打印、球体和精确切割肝切片培养以及微流控生物反应器的最新进展肯定会在不久的将来导致有效的肝纤维化体外 3D 模型。
