title: Isolation of novel multipotent neural crest-derived stem cells from adult human inferior turbinate.
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, p75(NTR), 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 p75(NTR) positive ITSCs that formed larger neurospheres and proliferated faster than p75(NTR) negative ITSCs. Taken together our study describes a novel, readily accessible source of multipotent human NCSCs for potential cell-replacement therapy.
authors: Molecular Neurobiology, University of Bielefeld, Bielefeld, Germany.
authors: Stefan
authors: S
authors: Hauser
authors: Darius
authors: D
authors: Widera
authors: Firas
authors: F
authors: Qunneis
authors: Janine
authors: J
authors: Müller
authors: Christin
authors: C
authors: Zander
authors: Johannes
authors: J
authors: Greiner
authors: Christina
authors: C
authors: Strauss
authors: Patrick
authors: P
authors: Lüningschrör
authors: Peter
authors: P
authors: Heimann
authors: Hartmut
authors: H
authors: Schwarze
authors: Jörg
authors: J
authors: Ebmeyer
authors: Holger
authors: H
authors: Sudhoff
authors: Marcos J
authors: MJ
authors: Araúzo-Bravo
authors: Boris
authors: B
authors: Greber
authors: Holm
authors: H
authors: Zaehres
authors: Hans
authors: H
authors: Schöler
authors: Christian
authors: C
authors: Kaltschmidt
authors: Barbara
authors: B
authors: Kaltschmidt
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051379:Mice; D016513:Mice, SCID; D008855:Microscopy, Electron, Scanning; D016253:Microscopy, Immunoelectron; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods; D014183:Transplantation, Heterologous; D014420:Turbinates / Q000166:cytology* / Q000378:metabolism
chemical_list: D007381:Intermediate Filament Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors