Chen Chen, Soto-Gutierrez Alejandro, Baptista Pedro M, Spee Bart
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; The Royal Netherlands Academy of Arts and Sciences, Hubrecht Institute and University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Gastroenterology. 2018 Apr;154(5):1258-1272. doi: 10.1053/j.gastro.2018.01.066. Epub 2018 Feb 8.
The incidence of liver disease is increasing globally. The only curative therapy for severe end-stage liver disease, liver transplantation, is limited by the shortage of organ donors. In vitro models of liver physiology have been developed and new technologies and approaches are progressing rapidly. Stem cells might be used as a source of liver tissue for development of models, therapies, and tissue-engineering applications. However, we have been unable to generate and maintain stable and mature adult liver cells ex vivo. We review factors that promote hepatocyte differentiation and maturation, including growth factors, transcription factors, microRNAs, small molecules, and the microenvironment. We discuss how the hepatic circulation, microbiome, and nutrition affect liver function, and the criteria for considering cells derived from stem cells to be fully mature hepatocytes. We explain the challenges to cell transplantation and consider future technologies for use in hepatic stem cell maturation, including 3-dimensional biofabrication and genome modification.
全球肝病发病率正在上升。严重终末期肝病的唯一治愈性疗法——肝移植，因器官供体短缺而受到限制。肝脏生理学的体外模型已经建立，新技术和方法也在迅速发展。干细胞可能用作肝脏组织的来源，用于模型开发、治疗以及组织工程应用。然而，我们一直无法在体外生成并维持稳定且成熟的成人肝细胞。我们综述了促进肝细胞分化和成熟的因素，包括生长因子、转录因子、微小RNA、小分子以及微环境。我们讨论了肝循环、微生物群和营养如何影响肝功能，以及将干细胞来源的细胞视为完全成熟肝细胞的标准。我们解释了细胞移植面临的挑战，并考虑了用于肝干细胞成熟的未来技术，包括三维生物制造和基因组修饰。
