Porcine Kidney Organoids Derived from Naïve-like Embryonic Stem Cells

Meishuang Li, Xiyun Guo, Linxin Cheng, Hong Zhang, Meng Zhou, Manling Zhang, Zhibao Yin, Tianxu Guo, Lihua Zhao, Han Liu, Xiubin Liang, Rongfeng Li
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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.
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从天真样胚胎干细胞中提取猪肾脏有组织细胞
供肾的稀缺性极大地影响了终末期肾衰竭患者的生存。猪越来越多地成为潜在的器官捐献者,但受到免疫排斥反应的限制。在利用 CHIR99021 和 FGF9 诱导策略已建立的人肾脏器官组织的基础上,我们用猪的天真样 ESCs(nESCs)生成了猪肾脏器官组织。生成的猪肾脏器官组织具有管状结构和基质成分。猪器官组织表达肾脏标记物,包括AQP1(近端肾小管)、WT1和PODO(荚膜细胞)以及CD31(血管内皮细胞)。这些结果表明,器官组织已发育出大部分肾细胞类型和结构,包括肾小球和近端肾小管。猪器官组织还被鉴定出具有右旋糖酐吸收功能。重要的是,猪器官组织具有一定数量的血管内皮细胞,这是研究免疫排斥反应的基础。衍生的猪器官组织可作为异种移植免疫抑制剂筛选的材料。
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