肾内科

JASN:肾脏干细胞新来源---早产儿尿液

作者:佚名 来源:生物谷 日期:2016-03-08
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         根据一项新的研究,从早产儿尿液中非侵入式收集的肾脏祖细胞(kidney progenitor cells, 也译作肾脏前体细胞)可能导致人们在针对肾病和肾损伤病人的再生性肾脏修复方面取得突破。相关研究结果于2016年3月3日在线发表在Journal of the American Society of Nephrology期刊上,论文标题为“Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells”。

      胎龄在37足周以前出生的活产婴儿称为早产儿(preterm infants)或未成熟儿。其出生体重大部分在2500g以下,头围在33cm以下。其器官功能和适应能力较足月儿为差者,应给予早产儿特殊护理。

  根据一项新的研究,从早产儿尿液中非侵入式收集的肾脏祖细胞(kidney progenitor cells, 也译作肾脏前体细胞)可能导致人们在针对肾病和肾损伤病人的再生性肾脏修复方面取得突破。相关研究结果于2016年3月3日在线发表在Journal of the American Society of Nephrology期刊上,论文标题为“Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells”。

  就人类而言,在怀孕大约34周后,肾脏发育就完成了,在此之后,肾细胞因自然老化、疾病或创伤而丢失。科学家们一直在寻找方法再生肾细胞,比如诱导其他类型的细胞表现出肾脏中这些细胞的过滤性质。

  为了解决这个问题,来自比利时天主教鲁汶大学的Elena Levtchenko博士、Fanny Oliveira Arcolino理科硕士及其同事们研究了健康成年人尿液中是否存在干细胞或肾脏祖细胞,然而,他们发现在肾脏成熟后,这些未分化的细胞非常罕见。“因此,我们认为早产婴儿的尿液可能是一种更好的替代选择,这是因为他们的肾脏仍然处于发育之中”, Levtchenko解释道,“我们收集了出生一天后的早产新生儿的尿液,结果发现在50%的情形下,尿液样品含有肾脏祖细胞。”这些祖细胞能够分化为成熟的肾细胞,而且也具有阻止细胞死亡的防御机制。

  作为Levtchenko博士实验室的一名博士生,Arcolino说,“早产新生儿肾脏祖细胞可能代表着一种强大的工具用于受损肾脏的细胞治疗和再生。”她也注意到一种被称作肾功能不全(renal insufficiency)---肾脏不能充分地过滤来自血液的废弃物---的疾病很可能是早产的结果。早产婴儿出生后,立即获得从其尿液中收集到的肾脏祖细胞,并利用它们作为一种治疗手段有可能挽救这些新生儿的生命。

  Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells

  doi:10.1681/ASN.2015060664

  Fanny Oliveira Arcolino*, Silvia Zia*, Katharina Held*, Elli Papadimitriou?, Koen Theunis?, Benedetta Bussolati?, Anke Raaijmakers*§, Karel Allegaert*‖, Thierry Voet?, Jan Deprest*§, Joris Vriens*, Jaan Toelen*§, Lambertus van den Heuvel*? and Elena Levtchenko

  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.

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