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[肝类器官:面临哪些挑战?]

[Hepatic organoids: What are the challenges?].

作者信息

Luce Eléanor, Messina Antonietta, Caillaud Amandine, Si-Tayeb Karim, Cariou Bertrand, Bur Etienne, Dubart-Kupperschmitt Anne, Duclos-Vallée Jean-Charles

机构信息

Inserm UMRS 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant Couturier, F-94800 Villejuif, France - Fédération hospitalo-universitaire Hépatinov, hôpital Paul Brousse, F-94800 Villejuif, France.

Université de Nantes, CHU Nantes, CNRS, Inserm, Institut du thorax, F-44000 Nantes, France.

出版信息

Med Sci (Paris). 2021 Oct;37(10):902-909. doi: 10.1051/medsci/2021119. Epub 2021 Oct 14.

Abstract

The study and understanding of liver organogenesis have allowed the development of protocols for pluripotent stem cells differentiation to overcome the lack of primary cells, providing an almost unlimited source of liver cells. However, as their differentiation in conventional 2D culture systems has shown serious limits, hepatic organoids derived from human pluripotent stem cells represent a promising alternative. These complex and organized structures, containing one or more cell types, make it possible to recapitulate in vitro some of the organ functions, thus enabling numerous applications such as the study of the liver development, the mass production of functional liver cells for transplantation or the development of bioartificial livers, as well as the in vitro modeling of hepatic pathologies allowing high throughput applications in drug screening or toxicity studies. Economic and ethical issues must also be taken into account before using these organoids in therapeutic applications.

摘要

对肝脏器官发生的研究和理解促使了多能干细胞分化方案的发展,以克服原代细胞的缺乏,提供几乎无限的肝细胞来源。然而,由于它们在传统二维培养系统中的分化显示出严重局限性,源自人类多能干细胞的肝类器官代表了一种有前景的替代方案。这些包含一种或多种细胞类型的复杂且有组织的结构,使得在体外重现部分器官功能成为可能,从而实现众多应用,如肝脏发育研究、用于移植的功能性肝细胞的大规模生产或生物人工肝的开发,以及肝脏疾病的体外建模,以允许在药物筛选或毒性研究中进行高通量应用。在将这些类器官用于治疗应用之前,还必须考虑经济和伦理问题。

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