Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease

EMBO Molecular Medicine

Orit Harari-Steinberg⁶  Sally Metsuyanim⁶  Dorit Omer⁶  Yehudit Gnatek⁶  Rotem Gershon⁶  Sara Pri-Chen⁶  Derya D. Ozdemir²  Yaniv Lerenthal⁷  Tzahi Noiman⁴  Herzel Ben-Hur³  Zvi Vaknin⁵  David F. Schneider⁵  Bruce J. Aronow¹  Ronald S. Goldstein⁴  Peter Hohenstein² 

[1] Division of Molecular and Developmental Biology, Department of Pediatrics, University of Cincinnati, Childrens Hospital Medical Center, Cincinnati, OH, USA;The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK;L.E.M. Laboratory of Early Detection, Nes Ziona, Israel;Mina and Everard Goodman Faculty of Life Sciences, Bar-IlanUniversity, Ramat-Gan, Israel;Department of Obstet and Gynecology, Assaf Harofeh, Tzrifin, Israel;The Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical Center, Ramat-Gan, Israel;Cancer Research Center, Sheba Medical Center, Ramat-Gan, Israel

关键词: development;    kidney stem cells;    progenitor cells;    regeneration;    stem cells;   

DOI  :  10.1002/emmm.201201584

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
Copyright © 2013 EMBO Molecular Medicine

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.