Nishinakamura Ryuichi, Sharmin Sazia, Taguchi Atsuhiro
Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
Pediatr Nephrol. 2017 Feb;32(2):195-200. doi: 10.1007/s00467-016-3339-z. Epub 2016 Feb 11.
Studies of kidney regeneration using stem cells have progressed rapidly in recent years. Our group has developed a protocol to induce nephron progenitors from both mouse and human pluripotent stem cells which is based on a revised model of early stage kidney specification. The induced progenitors readily reconstitute three-dimensional nephron structures, including glomeruli and renal tubules, in vitro. We can further generate human induced pluripotent stem cells (iPSCs), in which nephrin-expressing glomerular podocytes are tagged with green fluorescent protein (GFP). The sorted GFP-positive cells retain the podocyte-specific molecular and structural features. Upon transplantation, mouse endothelial cells of the host animals are integrated into the human iPSC-derived glomeruli, and the podocytes show further maturation. Other laboratories have reported different protocols to induce nephron structures from human iPSCs in vitro. These findings will accelerate our understanding of kidney development and diseases in humans.
近年来,利用干细胞进行肾脏再生的研究进展迅速。我们的团队基于早期肾脏特化的修订模型,开发了一种从小鼠和人类多能干细胞诱导肾祖细胞的方案。诱导产生的祖细胞能够在体外轻易地重建包括肾小球和肾小管在内的三维肾单位结构。我们还能进一步生成人类诱导多能干细胞(iPSC),其中表达nephrin的肾小球足细胞用绿色荧光蛋白(GFP)进行标记。分选得到的GFP阳性细胞保留了足细胞特异性的分子和结构特征。移植后,宿主动物的小鼠内皮细胞整合到人类iPSC来源的肾小球中,足细胞进一步成熟。其他实验室也报道了不同的方案来在体外从人类iPSC诱导生成肾单位结构。这些发现将加速我们对人类肾脏发育和疾病的理解。