Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells
Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells
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DOI：
10.1681/asn.2015060664
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发表时间：
2016-09-01
影响因子：
13.6
通讯作者：
Levtchenko, Elena
中科院分区：
文献类型：
--
作者：
Arcolino, Fanny Oliveira;Zia, Silvia;Levtchenko, Elena
在人类中，肾脏发生是在产前完成的，直到34周时肾单位才形成。我们假设，在肾脏发育完成之前出生的早产儿的尿液是高潜能干细胞/祖细胞的非侵入性来源。为了验证这一假设，我们收集了31-36周出生的新生儿在出生后第1天的新鲜尿液，并使用单细胞RT-PCR策略进行基因表达分析，并使用流式细胞术和免疫荧光技术进行蛋白质表达分析。新生儿干细胞/祖细胞表达肾单位祖细胞的标记，也表达基质祖细胞的标记，许多单个细胞共表达这些标记。此外，这些细胞表现出间充质干细胞的特征，并保护共培养的小管细胞免受顺铂诱导的凋亡。从新生儿干/祖细胞分化而来的足细胞表现为足细胞特异性基因和蛋白上调，白蛋白内吞，并通过足细胞特异性瞬时受体电位阳离子通道C亚家族成员6进行钙内流。分化的近端小管细胞表现为特异性基因上调和P-糖蛋白活性显著升高。我们认为，早产儿的尿液是一种新的非侵入性来源的肾祖细胞，能够分化为成熟的肾脏细胞，具有很高的再生肾修复潜力。
In humans, nephrogenesis is completed prenatally, with nephrons formed until 34 weeks of gestational age. We hypothesized that urine of preterm neonates born before the completion of nephrogenesis is a noninvasive source of highly potent stem/progenitor cells. To test this hypothesis, we collected freshly voided urine at day 1 after birth from neonates born at 31-36 weeks of gestational age and characterized isolated cells using a single cell RT-PCR strategy for gene expression analysis and flow cytometry and immunofluorescence for protein expression analysis. Neonatal stem/progenitor cells expressed markers of nephron progenitors but also, stromal progenitors, with many single cells coexpressing these markers. Furthermore, these cells presented mesenchymal stem cell features and protected cocultured tubule cells from cisplatin-induced apoptosis. Podocytes differentiated from the neonatal stem/progenitor cells showed upregulation of podocyte-specific genes and proteins, albumin endocytosis, and calcium influx via podocyte specific transient receptor potential cation channel, subfamily C, member 6. Differentiated proximal tubule cells showed upregulation of specific genes and significantly elevated p-glycoprotein activity. We conclude that urine of preterm neonates is a novel noninvasive source of kidney progenitors that are capable of differentiation into mature kidney cells and have high potential for regenerative kidney repair.