Adult palatum as a novel source of neural crest-related stem cells.
Somatic neural and neural crest stem cells are promising sources for cellular therapy of several neurodegenerative diseases. However, because of practical considerations such as inadequate accessibility of the source material, the application of neural crest stem cells is strictly limited. The secondary palate is a highly regenerative and heavily innervated tissue, which develops embryonically under direct contribution of neural crest cells. Here, we describe for the first time the presence of nestin-positive neural crest-related stem cells within Meissner corpuscles and Merkel cell-neurite complexes located in the hard palate of adult Wistar rats. After isolation, palatal neural crest-related stem cells (pNC-SCs) were cultivated in the presence of epidermal growth factor and fibroblast growth factor under serum-free conditions, resulting in large amounts of neurospheres. We used immunocytochemical techniques and reverse transcriptase-polymerase chain reaction to assess the expression profile of pNC-SCs. In addition to the expression of neural crest stem cell markers such as Nestin, Sox2, and p75, we detected the expression of Klf4, Oct4, and c-Myc. pNC-SCs differentiated efficiently into neuronal and glial cells. Finally, we investigated the potential expression of stemness markers within the human palate. We identified expression of stem cell markers nestin and CD133 and the transcription factors needed for reprogramming of somatic cells into pluripotent cells: Sox2, Oct4, Klf4, and c-Myc. These data show that cells isolated from palatal rugae form neurospheres, are highly plastic, and express neural crest stem cell markers. In addition, pNC-SCs may have the ability to differentiate into functional neurons and glial cells, serving as a starting point for therapeutic studies.
Widera
Darius
D
Institute of Cell Biology, Faculty of Biology, University of Bielefeld, Bielefeld, Germany.
Zander
Christin
C
Heidbreder
Meike
M
Kasperek
Yvonne
Y
Noll
Thomas
T
Seitz
Oliver
O
Saldamli
Belma
B
Sudhoff
Holger
H
Sader
Robert
R
Kaltschmidt
Christian
C
Kaltschmidt
Barbara
B
D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D000090062:Kruppel-Like Factor 4; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D064231:Nestin; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D010159:Palate / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
D007381:Intermediate Filament Proteins; C000715467:KLF4 protein, human; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D004247:DNA