These authors contributed equally to this work.
Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease
Article first published online: 2 SEP 2013
Copyright © 2013 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 10, pages 1556–1568, October 2013
How to Cite
Harari-Steinberg, O., Metsuyanim, S., Omer, D., Gnatek, Y., Gershon, R., Pri-Chen, S., Ozdemir, D. D., Lerenthal, Y., Noiman, T., Ben-Hur, H., Vaknin, Z., Schneider, D. F., Aronow, B. J., Goldstein, R. S., Hohenstein, P. and Dekel, B. (2013), Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease. EMBO Mol Med, 5: 1556–1568. doi: 10.1002/emmm.201201584
- Issue published online: 2 OCT 2013
- Article first published online: 2 SEP 2013
- Manuscript Accepted: 31 JUL 2013
- Manuscript Revised: 29 JUL 2013
- Manuscript Received: 22 MAY 2012
- Wolfson Clore Mayer, ISF. Grant Number: 1139/07
- kidney stem cells;
- progenitor cells;
- stem cells
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.