Abstract:
The scarcity of donor kidneys greatly impacts the survival of patients with end-stage renal failure. Pigs are increasingly becoming potential organ donors but are limited by immunological rejection. Based on the human kidney organoid already established with the CHIR99021 and FGF9 induction strategy, we generated porcine kidney organoids from porcine naïve-like ESCs (nESCs). The derived porcine organoids had a tubule-like constructure and matrix components. The porcine organoids expressed renal markers including AQP1 (proximal tubule), WT1 and PODO (podocyte), and CD31 (vascular endothelial cells). These results imply that the organoids had developed the majority of the renal cell types and structures, including glomeruli and proximal tubules. The porcine organoids were also identified to have a dextran absorptive function. Importantly, porcine organoids have a certain abundance of vascular endothelial cells, which are the basis for investigating immune rejection. The derived porcine organoids might serve as materials for immunosuppressor screening for xenotransplantation.
摘要:
供体肾脏的匮乏极大地影响了终末期肾衰竭患者的生存。猪越来越成为潜在的器官供体,但受到免疫排斥的限制。基于已经通过CHIR99021和FGF9诱导策略建立的人类肾脏类器官,我们从猪原始样ESC(nESC)产生了猪肾脏类器官。衍生的猪类器官具有小管样结构和基质组分。猪的类器官表达了肾脏标志物,包括AQP1(近端小管),WT1和PODO(足细胞),和CD31(血管内皮细胞)。这些结果表明,类器官已经发展了大多数肾细胞类型和结构,包括肾小球和近端小管。猪类器官也被鉴定为具有葡聚糖吸收功能。重要的是,猪的类器官有一定丰富的血管内皮细胞,这是研究免疫排斥反应的基础。来源于猪的类器官可作为异种移植的免疫抑制剂筛选材料。