C-Kit+ Cells Isolated from Developing Kidneys Are a Novel Population of Stem Cells with Regenerative Potential

Authors

  • Erika B. Rangel,

    1. Interdisciplinary Stem Cell Institute, São Paulo, São Paulo, Brazil
    2. Sociedade Beneficente Albert Einstein, Albert Einstein Hospital, São Paulo, São Paulo, Brazil
    3. Division of Nephrology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, Brazil
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  • Samirah A. Gomes,

    1. Interdisciplinary Stem Cell Institute, São Paulo, São Paulo, Brazil
    2. Division of Nephrology, Department of Medicine, Federal University of São Paulo, São Paulo, São Paulo, Brazil
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  • Raul A. Dulce,

    1. Interdisciplinary Stem Cell Institute, São Paulo, São Paulo, Brazil
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  • Courtney Premer,

    1. Interdisciplinary Stem Cell Institute, São Paulo, São Paulo, Brazil
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  • Claudia O. Rodrigues,

    1. Interdisciplinary Stem Cell Institute, São Paulo, São Paulo, Brazil
    2. Department of Molecular and Cellular Pharmacology, University of Miami, Miami, Florida, USA
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  • Rosemeire M. Kanashiro-Takeuchi,

    1. Interdisciplinary Stem Cell Institute, São Paulo, São Paulo, Brazil
    2. Department of Molecular and Cellular Pharmacology, University of Miami, Miami, Florida, USA
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  • Behzad Oskouei,

    1. Interdisciplinary Stem Cell Institute, São Paulo, São Paulo, Brazil
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  • Decio A. Carvalho,

    1. Interdisciplinary Stem Cell Institute, São Paulo, São Paulo, Brazil
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  • Phillip Ruiz,

    1. Departments of Surgery and Pathology, University of Miami, Miami, Florida, USA
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  • Jochen Reiser,

    1. Division of Nephrology and Hypertension, University of Miami, Miami, Florida, USA
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  • Joshua M. Hare

    Corresponding author
    1. Interdisciplinary Stem Cell Institute, São Paulo, São Paulo, Brazil
    2. Department of Molecular and Cellular Pharmacology, University of Miami, Miami, Florida, USA
    3. Division of Cardiology, Department of Medicine, Leonard M Miller School of Medicine, University of Miami, Miami, Florida, USA
    • Interdisciplinary Stem Cell Institute, Biomedical Research Bldg, University of Miami, 1501 NW Tenth Avenue, Room 908, Miami, Florida 33136, USA===

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    • Telephone: +1-305-243-5579; Fax: +1-305-243-5584


  • Author contributions: E.B.R.: conception and design, data collection and analysis, and manuscript writing; S.A.G. and R.A.D.: conception and design and data collection and analysis; C.P., R.M.K.T., B.O., and D.A.C.: data collection; C.O.R.: conception and design; P.R.: data analysis. J.R.: manuscript writing; J.M.H.: conception and design and manuscript writing.

Abstract

The presence of tissue specific precursor cells is an emerging concept in organ formation and tissue homeostasis. Several progenitors are described in the kidneys. However, their identity as a true stem cell remains elusive. Here, we identify a neonatal kidney-derived c-kit+ cell population that fulfills all of the criteria as a stem cell. These cells were found in the thick ascending limb of Henle's loop and exhibited clonogenicity, self-renewal, and multipotentiality with differentiation capacity into mesoderm and ectoderm progeny. Additionally, c-kit+ cells formed spheres in nonadherent conditions when plated at clonal density and expressed markers of stem cells, progenitors, and differentiated cells. Ex vivo expanded c-kit+ cells integrated into several compartments of the kidney, including tubules, vessels, and glomeruli, and contributed to functional and morphological improvement of the kidney following acute ischemia-reperfusion injury in rats. Together, these findings document a novel neonatal rat kidney c-kit+ stem cell population that can be isolated, expanded, cloned, differentiated, and used for kidney repair following acute kidney injury. These cells have important biological and therapeutic implications. STEM Cells 2013;31:1644–1656

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