MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, EH16 4UU, UK.
Centre for Liver Research, Institute of Immunology and Immunotherapy and National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK.
Arch Toxicol. 2018 Oct;92(10):3117-3129. doi: 10.1007/s00204-018-2280-2. Epub 2018 Aug 28.
Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to the shortage of donor organs. Developing renewable sources of human liver tissue is therefore attractive. Pluripotent stem cell-derived liver tissue represents a potential alternative to cadaver derived hepatocytes and whole organ transplant. At present, two-dimensional differentiation procedures deliver tissue lacking certain functions and long-term stability. Efforts to overcome these limiting factors have led to the building of three-dimensional (3D) cellular aggregates. Although enabling for the field, their widespread application is limited due to their reliance on variable biological components. Our studies focused on the development of 3D liver tissue under defined conditions. In vitro generated 3D tissues exhibited stable phenotype for over 1 year in culture, providing an attractive resource for long-term in vitro studies. Moreover, 3D derived tissue provided critical liver support in two animal models, including immunocompetent recipients. Therefore, we believe that our study provides stable human tissue to better model liver biology 'in the dish', and in the future may permit the support of compromised liver function in humans.
肝脏疾病是一个不断加剧的全球健康问题。虽然肝移植是一种有效的治疗方式，但由于供体器官短缺，患者死亡率有所上升。因此，开发可再生的人类肝脏组织具有吸引力。多能干细胞衍生的肝组织代表了一种替代尸体来源的肝细胞和整个器官移植的潜在方法。目前，二维分化程序提供的组织缺乏某些功能和长期稳定性。为了克服这些限制因素，人们努力构建三维（3D）细胞聚集体。尽管这为该领域提供了支持，但由于它们依赖于可变的生物成分，其广泛应用受到限制。我们的研究重点是在明确条件下开发 3D 肝脏组织。在体外生成的 3D 组织在培养中稳定表型超过 1 年，为长期体外研究提供了有吸引力的资源。此外，3D 衍生的组织在包括免疫功能正常的受者在内的两种动物模型中提供了关键的肝脏支持。因此，我们认为我们的研究提供了稳定的人类组织，以更好地在“培养皿”中模拟肝脏生物学，并且在未来可能允许支持人类受损的肝功能。
