腎內科

JASN:腎髒幹細胞新來源---早產兒尿液

作者:佚名 來源:生物穀 日期:2016-03-08
導讀

         根據一項新的研究,從早產兒尿液中非侵入式收集的腎髒祖細胞(kidney progenitor cells, 也譯作腎髒前體細胞)可能導致人們在針對腎病和腎損傷病人的再生性腎髒修複方麵取得突破。相關研究結果於2016年3月3日在線發表在Journal of the American Society of Nephrology期刊上,論文標題為“Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells”。

      胎齡在37足周以前出生的活產嬰兒稱為早產兒(preterm infants)或未成熟兒。其出生體重大部分在2500g以下,頭圍在33cm以下。其器官功能和適應能力較足月兒為差者,應給予早產兒特殊護理。

  根據一項新的研究,從早產兒尿液中非侵入式收集的腎髒祖細胞(kidney progenitor cells, 也譯作腎髒前體細胞)可能導致人們在針對腎病和腎損傷病人的再生性腎髒修複方麵取得突破。相關研究結果於2016年3月3日在線發表在Journal of the American Society of Nephrology期刊上,論文標題為“Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells”。

  就人類而言,在懷孕大約34周後,腎髒發育就完成了,在此之後,腎細胞因自然老化、疾病或創傷而丟失。科學家們一直在尋找方法再生腎細胞,比如誘導其他類型的細胞表現出腎髒中這些細胞的過濾性質。

  為了解決這個問題,來自比利時天主教魯汶大學的Elena Levtchenko博士、Fanny Oliveira Arcolino理科碩士及其同事們研究了健康成年人尿液中是否存在幹細胞或腎髒祖細胞,然而,他們發現在腎髒成熟後,這些未分化的細胞非常罕見。“因此,我們認為早產嬰兒的尿液可能是一種更好的替代選擇,這是因為他們的腎髒仍然處於發育之中”, Levtchenko解釋道,“我們收集了出生一天後的早產新生兒的尿液,結果發現在50%的情形下,尿液樣品含有腎髒祖細胞。”這些祖細胞能夠分化為成熟的腎細胞,而且也具有阻止細胞死亡的防禦機製。

  作為Levtchenko博士實驗室的一名博士生,Arcolino說,“早產新生兒腎髒祖細胞可能代表著一種強大的工具用於受損腎髒的細胞治療和再生。”她也注意到一種被稱作腎功能不全(renal insufficiency)---腎髒不能充分地過濾來自血液的廢棄物---的疾病很可能是早產的結果。早產嬰兒出生後,立即獲得從其尿液中收集到的腎髒祖細胞,並利用它們作為一種治療手段有可能挽救這些新生兒的生命。

  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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