Abstract

Adult human neural crest-derived stem cells (NCSCs) are of extraordinary high plasticity and promising candidates for the use in regenerative medicine. Here we describe for the first time a novel neural crest-derived stem cell population within the respiratory epithelium of human adult inferior turbinate. In contrast to superior and middle turbinates, high amounts of source material could be isolated from human inferior turbinates. Using minimally-invasive surgery methods isolation is efficient even in older patients.
Within their endogenous niche, inferior turbinate stem cells (ITSCs) expressed high levels of nestin, p75NTR, and S100. Immunoelectron microscopy using anti-p75 antibodies displayed that ITSCs are of glial origin and closely related to nonmyelinating Schwann cells. Cultivated ITSCs were positive for nestin and S100 and the neural crest markers Slug and SOX10. Whole genome microarray analysis showed pronounced differences to human ES cells in respect to pluripotency markers OCT4, SOX2, LIN28, and NANOG, whereas expression of WDR5, KLF4, and c-MYC was nearly similar. ITSCs were able to differentiate into cells with neuro-ectodermal and mesodermal phenotype. Additionally ITSCs are able to survive and perform neural crest typical chain migration in vivo when transplanted into chicken embryos. However ITSCs do not form teratomas in severe combined immunodeficient mice. Finally, we developed a separation strategy based on magnetic cell sorting of p75NTR positive ITSCs that formed larger neurospheres and proliferated faster than p75NTR negative ITSCs. Taken together our study describes a novel, readily accessible source of multipotent human NCSCs for potential cell-replacement therapy.

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cover image Stem Cells and Development
Stem Cells and Development
Volume 21Issue Number 5March 20, 2012
Pages: 742 - 756
PubMed: 22128806

History

Published in print: March 20, 2012
Published ahead of print: 26 January 2012
Published online: 30 November 2011
Accepted: 30 November 2011
Received: 1 August 2011

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    Authors

    Affiliations

    Stefan Hauser
    Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany.
    Darius Widera
    Cell Biology, University of Bielefeld, Bielefeld, Germany.
    Firas Qunneis
    Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany.
    Janine Müller
    Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany.
    Christin Zander
    Cell Biology, University of Bielefeld, Bielefeld, Germany.
    Johannes Greiner
    Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany.
    Christina Strauss
    Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany.
    Patrick Lüningschrör
    Cell Biology, University of Bielefeld, Bielefeld, Germany.
    Peter Heimann
    Cell Biology, University of Bielefeld, Bielefeld, Germany.
    Hartmut Schwarze
    Klinik für Hals-, Nasen- und Ohrenheilkunde, Kopf- und Halschirurgie, Bielefeld, Germany.
    Jörg Ebmeyer
    Klinik für Hals-, Nasen- und Ohrenheilkunde, Kopf- und Halschirurgie, Bielefeld, Germany.
    Holger Sudhoff
    Klinik für Hals-, Nasen- und Ohrenheilkunde, Kopf- und Halschirurgie, Bielefeld, Germany.
    Marcos J. Araúzo-Bravo
    Department Cell and Developmental Biology, Max-Planck-Institute for Molecular Medicine, Münster, Germany.
    Boris Greber
    Department Cell and Developmental Biology, Max-Planck-Institute for Molecular Medicine, Münster, Germany.
    Holm Zaehres
    Department Cell and Developmental Biology, Max-Planck-Institute for Molecular Medicine, Münster, Germany.
    Hans Schöler
    Department Cell and Developmental Biology, Max-Planck-Institute for Molecular Medicine, Münster, Germany.
    Christian Kaltschmidt
    Cell Biology, University of Bielefeld, Bielefeld, Germany.
    Barbara Kaltschmidt
    Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany.

    Notes

    Address correspondence to:Dr. Barbara KaltschmidtMolecular NeurobiologyUniversity of BielefeldUniversitätsstr. 25D-33501 BielefeldGermany
    E-mail: [email protected]

    Author Disclosure Statement

    No competing financial interests exists.

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