title: Schwann cells can be reprogrammed to multipotency by culture.
abstract: Adult neural crest related-stem cells persist in adulthood, making them an ideal and easily accessible source of multipotent cells for potential clinical use. Recently, we reported the presence of neural crest-related stem cells within adult palatal ridges, thus raising the question of their localization in their endogenous niche. Using immunocytochemistry, reverse transcription-polymerase chain reaction, and correlative fluorescence and transmission electron microscopy, we identified myelinating Schwann cells within palatal ridges as a putative neural crest stem cell source. Palatal Schwann cells expressed nestin, p75(NTR), and S100. Correlative fluorescence and transmission electron microscopy revealed the exclusive nestin expression within myelinating Schwann cells. Palatal neural crest stem cells and nestin-positive Schwann cells isolated from adult sciatic nerves were able to grow under serum-free conditions as neurospheres in presence of FGF-2 and EGF. Spheres of palatal and sciatic origin showed overlapping expression pattern of neural crest stem cell and Schwann cell markers. Expression of the pluripotency factors Sox2, Klf4, c-Myc, Oct4, the NF-κB subunits p65, p50, and the NF-κB-inhibitor IκB-β were up-regulated in conventionally cultivated sciatic nerve Schwann cells and in neurosphere cultures. Finally, neurospheres of palatal and sciatic origin were able to differentiate into ectodermal, mesodermal, and endodermal cell types emphasizing their multipotency. Taken together, we show that nestin-positive myelinating Schwann cells can be reprogrammed into multipotent adult neural crest stem cells under appropriate culture conditions.
authors.affiliation: Department of Cell Biology, University of Bielefeld, Bielefeld, Germany.
authors.forename: Darius
authors.initials: D
authors.lastname: Widera
authors.forename: Peter
authors.initials: P
authors.lastname: Heimann
authors.forename: Christin
authors.initials: C
authors.lastname: Zander
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Imielski
authors.forename: Meike
authors.initials: M
authors.lastname: Heidbreder
authors.forename: Mike
authors.initials: M
authors.lastname: Heilemann
authors.forename: Christian
authors.initials: C
authors.lastname: Kaltschmidt
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaltschmidt
mesh_terms: D000818:Animals; D002449:Cell Aggregation; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D002999:Clone Cells; D007381:Intermediate Filament Proteins / Q000378:metabolism / Q000648:ultrastructure; D019394:Ki-67 Antigen / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D009092:Mucous Membrane / Q000166:cytology; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D009185:Myelin Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D016328:NF-kappa B / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000648:ultrastructure; D064231:Nestin; D009432:Neural Crest / Q000166:cytology; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D010159:Palate / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D009185:Myelin Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; C489546:Pmp22 protein, rat; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D009418:S100 Proteins; C068313:Ngfr protein, rat