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Human skin-derived stem cells migrate throughout forebrain and differentiate into astrocytes after injection into adult mouse brain

Authors

  • Marzia Belicchi,

    1. Department of Neurological Sciences, Stem Cell Laboratory, Centro Dino Ferrari, IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
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    • The first two authors contributed equally to this work.

  • Federica Pisati,

    1. Department of Neurological Sciences, Stem Cell Laboratory, Centro Dino Ferrari, IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
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    • The first two authors contributed equally to this work.

  • Raffaella Lopa,

    1. Centro Trasfusionale e di Immunologia dei Trapianti, Ospedale Maggiore Policlinico, Milan, Italy
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  • Laura Porretti,

    1. Centro Trasfusionale e di Immunologia dei Trapianti, Ospedale Maggiore Policlinico, Milan, Italy
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  • Francesco Fortunato,

    1. Department of Neurological Sciences, Stem Cell Laboratory, Centro Dino Ferrari, IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
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  • Manuela Sironi,

    1. IRCCS Eugenio Medea, Bosisio Parini, Italy
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  • Mario Scalamogna,

    1. Centro Trasfusionale e di Immunologia dei Trapianti, Ospedale Maggiore Policlinico, Milan, Italy
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  • Eugenio A. Parati,

    1. Laboratory of Neuropharmacology, National Neurological Institute “C. Besta,” Milan, Italy
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  • Nereo Bresolin,

    1. Department of Neurological Sciences, Stem Cell Laboratory, Centro Dino Ferrari, IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
    2. IRCCS Eugenio Medea, Bosisio Parini, Italy
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  • Yvan Torrente

    Corresponding author
    1. Department of Neurological Sciences, Stem Cell Laboratory, Centro Dino Ferrari, IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
    2. IRCCS Eugenio Medea, Bosisio Parini, Italy
    • Stem Cell Laboratory, Department of Neurological Science, Padiglione Ponti, Ospedale Policlinico, via Francesco Sforza 35, 20122 Milan, Italy
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Abstract

Recent evidence indicates that neural stem cell properties can be found among a mammalian skin-derived multipotent population. A major barrier in the further characterization of the human skin-derived neural progenitors is the inability to isolate this population based on expression of cell surface markers. Our work has been devoted to purified human skin-derived stem cells that are capable of neural differentiation, based on the presence or absence of the AC133 cell surface marker. The enriched skin-derived AC133+ cells express the CD34 and Thy-1 antigens. These cells cultured in a growth medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) proliferate, forming spheres, and differentiate in vitro into neurons, astrocytes, and rarely into oligodendrocytes. Single cells from sphere cultures initiated from human purified AC133+ cells were replated as single cells and were able to generate new spheres, demonstrating the self-renewing ability of these stem cell populations. Brain engraftment of cells obtained from human purified AC133+-derived spheres generated different neural phenotypes: immature neurons and a most abundant population of well differentiated astrocytes. The AC133-derived astrocytes assumed perivascular locations in the frontal cortex. No donor-derived oligodendrocytes were found in the transplanted mouse brains. Several donor small, rounded cells that expressed endothelial markers were found close to the host vessel and near the subventricular zone. Thus, mammalian skin AC133-derived cells behave as a multipotent population with the capacity to differentiate into neural lineages in vitro and, prevalently, endothelium and astrocytes in vivo, demonstrating the great plasticity of these cells and suggesting potential clinical application. © 2004 Wiley-Liss, Inc.

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