Department of Surgery.
Department of Pathology, University of Pittsburgh School of Medicine.
Curr Opin Gastroenterol. 2021 May 1;37(3):224-230. doi: 10.1097/MOG.0000000000000726.
In this review, we will explore recent advances in human induced pluripotent stem cell (iPSC)-based modeling of metabolic liver disease and biofabrication of synthetic human liver tissue while also discussing the emerging concept of synthetic biology to generate more physiologically relevant liver disease models.
iPSC-based platforms have facilitated the study of underlying cellular mechanisms and potential therapeutic strategies for a number of metabolic liver diseases. Concurrently, rapid progress in biofabrication and gene editing technologies have led to the generation of human hepatic tissue that more closely mimic the complexity of the liver.
iPSC-based liver tissue is rapidly becoming available for modeling liver physiology due to its ability to recapitulate the complex three-dimensional architecture of the liver and recapitulate interactions between the different cell types and their surroundings. These mini livers have also been used to recapitulate liver disease pathways using the tools of synthetic biology, such as gene editing, to control gene circuits. Further development in this field will undoubtedly bolster future investigations not only in disease modeling and basic research, but also in personalized medicine and autologous transplantation.
在这篇综述中，我们将探讨基于人诱导多能干细胞（iPSC）的代谢性肝病模型和合成人肝组织的生物制造的最新进展，同时讨论新兴的合成生物学概念，以生成更具生理相关性的肝病模型。
基于 iPSC 的平台促进了许多代谢性肝病的基础细胞机制和潜在治疗策略的研究。同时，生物制造和基因编辑技术的快速进步导致了更能模拟肝脏复杂性的人类肝组织的产生。
由于能够重现肝脏的复杂三维结构和不同细胞类型及其周围环境之间的相互作用，基于 iPSC 的肝组织正迅速成为模拟肝脏生理学的工具。这些迷你肝脏也已被用于使用合成生物学工具（如基因编辑）来控制基因回路，再现肝脏疾病途径。该领域的进一步发展无疑将推动未来的研究，不仅在疾病建模和基础研究方面，而且在个性化医学和自体移植方面。
