Induction of neuronal differentiation of adult human olfactory neuroepithelial-derived progenitors.
Neurosphere forming cells (NSFCs) have been established from cultures of adult olfactory neuroepithelium obtained from patients and cadavers as described previously. They remained undifferentiated in serum or defined media with or without neurotrophic factors. Many factors affect the differentiation of stem cells along a neuronal pathway. Retinoic acid (RA), forskolin (FN), and sonic hedgehog (Shh) have been reported to act as growth promoters during neurogenesis of embryonic CNS in vivo. The effect of RA, FN, and Shh on NSFCs' neuronal lineage restriction has not been described. The application of RA, FN, and Shh to NSFCs induced the expression of motoneuronal transcription factors, tyrosine hydroxylase, an indicator of dopamine production, and neurite formation. These studies further heighten the potential for using olfactory neuroepithelial progenitors for future autologous cell replacement strategies in neurodegenerative conditions and trauma as well as for use in diagnostic evaluation.
Zhang
Xiaodong
X
Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, 500 South Preston Street, Louisville, KY 40202, USA.
Klueber
Kathleen M
KM
Guo
Zhanfang
Z
Cai
Jun
J
Lu
Chengliang
C
Winstead
Welby I
WI
Qiu
Mengsheng
M
Roisen
Fred J
FJ
D000328:Adult; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018920:Coculture Techniques / Q000379:methods; D005576:Colforsin / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins; D006801:Humans; D007211:Indoles; D008297:Male; D032342:Muscle Cells / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009831:Olfactory Mucosa / Q000166:cytology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D016704:Synapsins / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D015534:Trans-Activators / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
D053823:Hedgehog Proteins; D007211:Indoles; C509239:SHH protein, human; C493459:SLC18A3 protein, human; D016704:Synapsins; D013778:Tetrazolium Salts; D013844:Thiazoles; D015534:Trans-Activators; D014157:Transcription Factors; D050494:Vesicular Acetylcholine Transport Proteins; D005576:Colforsin; C007293:DAPI; D014212:Tretinoin; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D010751:Phosphopyruvate Hydratase; C022616:thiazolyl blue