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Engineering in vitro models of hepatofibrogenesis
Advanced Drug Delivery Reviews ( IF 16.1 ) Pub Date : 2017-05-31 , DOI: 10.1016/j.addr.2017.05.018
Giuseppe Mazza , Walid Al-Akkad , Krista Rombouts

Chronic liver disease is a major cause of morbidity and mortality worldwide marked by chronic inflammation and fibrosis/scarring, resulting in end-stage liver disease and its complications. Hepatic stellate cells (HSCs) are a dominant contributor to liver fibrosis by producing excessive extracellular matrix (ECM), irrespective of the underlying disease aetiologies, and for many decades research has focused on the development of a number of anti-fibrotic strategies targeting this cell. Despite major improvements in two-dimensional systems (2D) by using a variety of cell culture models of different complexity, an efficient anti-fibrogenic therapy has yet to be developed. The development of well-defined three-dimensional (3D) in vitro models, which mimic ECM structures as found in vivo, have demonstrated the importance of cell-matrix bio-mechanics, the complex interactions between HSCs and hepatocytes and other non-parenchymal cells, and this to improve and promote liver cell-specific functions. Henceforth, refinement of these 3D in vitro models, which reproduce the liver microenvironment, will lead to new objectives and to a possible new era in the search for antifibrogenic compounds.



中文翻译:

肝纤维化工程体外模型

慢性肝病是世界范围内以慢性炎症和纤维化/瘢痕形成为特征的发病率和死亡率的主要原因,导致终末期肝病及其并发症。肝星状细胞(HSC)通过产生过量的细胞外基质(ECM)成为肝纤维化的主要贡献者,无论潜在的疾病病因如何,数十年来的研究集中在针对该细胞的多种抗纤维化策略的开发上。尽管通过使用各种复杂程度不同的细胞培养模型对二维系统(2D)进行了重大改进,但尚未开发出有效的抗纤维化疗法。定义明确的三维(3D)体外模型的开发,该模型模仿体内发现的ECM结构,已经证明了细胞基质生物力学的重要性,HSC与肝细胞和其他非实质细胞之间复杂的相互作用,以及改善和促进肝细胞特异性功能的重要性。今后,对这些能够再现肝脏微环境的3D体外模型的改进将导致寻找抗纤维化化合物的新目标和可能的新时代。

更新日期:2017-05-31
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