Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA; Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Cell Rep. 2020 Jun 2;31(9):107711. doi: 10.1016/j.celrep.2020.107711.
The availability of an autologous transplantable auxiliary liver would dramatically affect the treatment of liver disease. Assembly and function in vivo of a bioengineered human liver derived from induced pluripotent stem cells (iPSCs) has not been previously described. By improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, we generated functional engineered human mini livers and performed transplantation in a rat model. Whereas previous studies recellularized liver scaffolds largely with rodent hepatocytes, we repopulated not only the parenchyma with human iPSC-hepatocytes but also the vascular system with human iPS-endothelial cells, and the bile duct network with human iPSC-biliary epithelial cells. The regenerated human iPSC-derived mini liver containing multiple cell types was tested in vivo and remained functional for 4 days after auxiliary liver transplantation in immunocompromised, engineered (IL2rg) rats.
自体可移植辅助肝脏的可用性将极大地影响肝病的治疗。以前没有描述过从诱导多能干细胞（iPSCs）衍生的生物工程化人类肝脏在体内的组装和功能。通过改进肝去细胞化、再细胞化和不同肝细胞谱系在类器官环境中的分化方法，我们生成了功能性工程化人类迷你肝脏，并在大鼠模型中进行了移植。以前的研究主要用鼠肝细胞再细胞化肝支架，而我们不仅用人类 iPSC-肝细胞填充实质，还用人 iPS 内皮细胞填充血管系统，用人 iPSC 胆管上皮细胞填充胆管网络。在免疫功能低下的工程化（IL2rg）大鼠中进行辅助性肝移植后 4 天，体内测试了含有多种细胞类型的再生人 iPSC 衍生的迷你肝脏，其仍保持功能。
