Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease
Open Access
- 2 September 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 5 (10), 1556-1568
- https://doi.org/10.1002/emmm.201201584
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.Keywords
This publication has 38 references indexed in Scilit:
- The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targetsEMBO Molecular Medicine, 2012
- Dedifferentiation of Foetal CNS Stem Cells to Mesendoderm-Like Cells through an EMT ProcessPLOS ONE, 2012
- Isolation and Expansion of Human Limbal Stromal Niche CellsInvestigative Opthalmology & Visual Science, 2012
- The GUDMAP database – an online resource for genitourinary researchDevelopment, 2011
- Concise Review: Kidney Stem/Progenitor Cells: Differentiate, Sort Out, or Reprogram?The International Journal of Cell Cloning, 2010
- Adriamycin Nephropathy: A Failure of Endothelial Progenitor Cell-Induced RepairThe American Journal of Pathology, 2010
- BMP7 promotes proliferation of nephron progenitor cells via a JNK-dependent mechanismDevelopment, 2009
- Expression of Stem Cell Markers in the Human Fetal KidneyPLOS ONE, 2009
- Six2 Defines and Regulates a Multipotent Self-Renewing Nephron Progenitor Population throughout Mammalian Kidney DevelopmentCell Stem Cell, 2008
- Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epitheliaDevelopmental Biology, 2007