title: Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells.
abstract: 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.
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Group of Biomedical Sciences and.
authors.forename: Fanny Oliveira
authors.initials: FO
authors.lastname: Arcolino
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Group of Biomedical Sciences and.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zia
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Group of Biomedical Sciences and.
authors.forename: Katharina
authors.initials: K
authors.lastname: Held
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy;
authors.forename: Elli
authors.initials: E
authors.lastname: Papadimitriou
authors.affiliation: Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium;
authors.forename: Koen
authors.initials: K
authors.lastname: Theunis
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy;
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bussolati
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Group of Biomedical Sciences and Department of Pediatrics and.
authors.forename: Anke
authors.initials: A
authors.lastname: Raaijmakers
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Group of Biomedical Sciences and Neonatal Intensive Care Unit, Universitaire Ziekenhuizen Leuven, Leuven, Belgium; and.
authors.forename: Karel
authors.initials: K
authors.lastname: Allegaert
authors.affiliation: Department of Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium;
authors.forename: Thierry
authors.initials: T
authors.lastname: Voet
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Group of Biomedical Sciences and Department of Pediatrics and.
authors.forename: Jan
authors.initials: J
authors.lastname: Deprest
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Group of Biomedical Sciences and.
authors.forename: Joris
authors.initials: J
authors.lastname: Vriens
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Group of Biomedical Sciences and Department of Pediatrics and.
authors.forename: Jaan
authors.initials: J
authors.lastname: Toelen
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Group of Biomedical Sciences and Department of Pediatric Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Lambertus
authors.initials: L
authors.lastname: van den Heuvel
authors.affiliation: Department of Development and Regeneration, Organ System Cluster, Group of Biomedical Sciences and Department of Pediatrics and elena.levtchenko@uzleuven.be.
authors.forename: Elena
authors.initials: E
authors.lastname: Levtchenko
mesh_terms: D002454:Cell Differentiation; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007668:Kidney / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D014556:Urine / Q000166:cytology*
keywords: preterm; stem cell; urine