title: Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease.
abstract: Identification of tissue-specific renal stem/progenitor cells with nephrogenic potential is a critical step in developing cell-based therapies for renal disease. In the human kidney, stem/progenitor cells are induced into the nephrogenic pathway to form nephrons until the 34 week of gestation, and no equivalent cell types can be traced in the adult kidney. Human nephron progenitor cells (hNPCs) have yet to be isolated. Here we show that growth of human foetal kidneys in serum-free defined conditions and prospective isolation of NCAM1(+) cells selects for nephron lineage that includes the SIX2-positive cap mesenchyme cells identifying a mitotically active population with in vitro clonogenic and stem/progenitor properties. After transplantation in the chick embryo, these cells-but not differentiated counterparts-efficiently formed various nephron tubule types. hNPCs engrafted and integrated in diseased murine kidneys and treatment of renal failure in the 5/6 nephrectomy kidney injury model had beneficial effects on renal function halting disease progression. These findings constitute the first definition of an intrinsic nephron precursor population, with major potential for cell-based therapeutic strategies and modelling of kidney disease.
authors.affiliation: The Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical Center, Ramat-Gan, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Harari-Steinberg
authors.forename: Sally
authors.initials: S
authors.lastname: Metsuyanim
authors.forename: Dorit
authors.initials: D
authors.lastname: Omer
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Gnatek
authors.forename: Rotem
authors.initials: R
authors.lastname: Gershon
authors.forename: Sara
authors.initials: S
authors.lastname: Pri-Chen
authors.forename: Derya D
authors.initials: DD
authors.lastname: Ozdemir
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Lerenthal
authors.forename: Tzahi
authors.initials: T
authors.lastname: Noiman
authors.forename: Herzel
authors.initials: H
authors.lastname: Ben-Hur
authors.forename: Zvi
authors.initials: Z
authors.lastname: Vaknin
authors.forename: David F
authors.initials: DF
authors.lastname: Schneider
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Goldstein
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenstein
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dekel
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009399:Nephrons / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000601:surgery*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D019002:CD56 Antigen; D018398:Homeodomain Proteins; C522918:NCAM1 protein, human; D009419:Nerve Tissue Proteins; C484762:SIX2 protein, human
keywords: development; kidney stem cells; progenitor cells; regeneration; stem cells