Abstract
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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged, 80 and over
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Analysis of Variance
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Animals
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cells, Cultured
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Chick Embryo
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Choline O-Acetyltransferase / metabolism
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Coculture Techniques / methods
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Colforsin / pharmacology
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Drug Interactions
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Female
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Gene Expression Regulation, Developmental / drug effects
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Hedgehog Proteins
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Humans
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Indoles
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Male
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Muscle Cells / physiology
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Neurites / drug effects
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Neurites / physiology
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Neurites / ultrastructure
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Neurons / drug effects
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Neurons / physiology*
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Neurons / ultrastructure
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Olfactory Mucosa / cytology*
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Phosphopyruvate Hydratase / metabolism
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Stem Cells / drug effects
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Stem Cells / physiology*
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Synapsins / metabolism
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Tetrazolium Salts
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Thiazoles
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Trans-Activators / pharmacology
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Transcription Factors / metabolism
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Tretinoin / pharmacology
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Tyrosine 3-Monooxygenase / metabolism
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Vesicular Acetylcholine Transport Proteins / metabolism
Substances
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Hedgehog Proteins
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Indoles
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SHH protein, human
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SLC18A3 protein, human
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Synapsins
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Tetrazolium Salts
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Thiazoles
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Trans-Activators
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Transcription Factors
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Vesicular Acetylcholine Transport Proteins
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Colforsin
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DAPI
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Tretinoin
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Tyrosine 3-Monooxygenase
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Choline O-Acetyltransferase
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Phosphopyruvate Hydratase
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thiazolyl blue