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

Authors

  • Orit Harari-Steinberg,

    1. The Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical Center, Ramat-Gan, Israel
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    • These authors contributed equally to this work.
  • Sally Metsuyanim,

    1. The Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical Center, Ramat-Gan, Israel
    2. Mina and Everard Goodman Faculty of Life Sciences, Bar-IlanUniversity, Ramat-Gan, Israel
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    • These authors contributed equally to this work.
  • Dorit Omer,

    1. The Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical Center, Ramat-Gan, Israel
    2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Yehudit Gnatek,

    1. The Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical Center, Ramat-Gan, Israel
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  • Rotem Gershon,

    1. The Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical Center, Ramat-Gan, Israel
    2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Sara Pri-Chen,

    1. The Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical Center, Ramat-Gan, Israel
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  • Derya D. Ozdemir,

    1. The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK
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  • Yaniv Lerenthal,

    1. Cancer Research Center, Sheba Medical Center, Ramat-Gan, Israel
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  • Tzahi Noiman,

    1. Mina and Everard Goodman Faculty of Life Sciences, Bar-IlanUniversity, Ramat-Gan, Israel
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  • Herzel Ben-Hur,

    1. L.E.M. Laboratory of Early Detection, Nes Ziona, Israel
    2. Department of Obstet and Gynecology, Assaf Harofeh, Tzrifin, Israel
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  • Zvi Vaknin,

    1. Department of Obstet and Gynecology, Assaf Harofeh, Tzrifin, Israel
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  • David F. Schneider,

    1. Department of Obstet and Gynecology, Assaf Harofeh, Tzrifin, Israel
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  • Bruce J. Aronow,

    1. Division of Molecular and Developmental Biology, Department of Pediatrics, University of Cincinnati, Childrens Hospital Medical Center, Cincinnati, OH, USA
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  • Ronald S. Goldstein,

    1. Mina and Everard Goodman Faculty of Life Sciences, Bar-IlanUniversity, Ramat-Gan, Israel
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  • Peter Hohenstein,

    1. The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, UK
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  • Benjamin Dekel

    Corresponding author
    1. The Pediatric Stem Cell Research Institute, Edmond and Lily Safra Children's Hospital, Sheba Center for Regenerative Medicine, Sheba Medical Center, Ramat-Gan, Israel
    2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    3. Division of Pediatric Nephrology, Edmond& Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel
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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.

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