title: Plasticity of rat bone marrow-derived 5-hydroxytryptamine-sensitive neurons: dedifferentiation and redifferentiation.
abstract: Inducing cellular dedifferentiation has been proposed as a potential method for enhancing endogenous regeneration in mammals. Here we demonstrate that phenotypic and functional neurons derived from adult rat bone marrow stromal stem cells (MSCs) can be induced to undergo dedifferentiation, then proliferation and redifferentiation. In addition to morphological changes and expression of neuronal markers, neuron-specific enolase and neurofilament H, functional differentiation was monitored by intracellular Ca2+ mobilization in response to a ubiquitous neurotransmitter, 5-hydroxytryptamine (5-HT) at different stages. The neurons derived from rMSCs were found to have increased 5-HT response. This 5-HT sensitivity could be reversed to basal level similar to that found in rMSCs when neurons, up to 3 days after neuronal induction, were induced to undergo dedifferentiation. Increase in 5-HT-induced Ca2+ mobilization was again observed when rMSCs derived from dedifferentiated neurons were induced to redifferentiate into neurons again. Variation in 5-HT1A receptor immunoreactivity was observed in stem cells, differentiated neurons, dedifferentiated neurons and redifferentiation neurons, consistent with their respective 5-HT sensitivity. These results suggest that adult bone marrow-derived 5-HT sensitive neurons are capable of dedifferentiation, then proliferation and redifferentiation, indicating their plasticity and potential use in treatment of neural degenerative diseases.
authors.affiliation: Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors.forename: Ting Yu
authors.initials: TY
authors.lastname: Li
authors.forename: Chang
authors.initials: C
authors.lastname: Shu
authors.forename: Connie Hau Yan
authors.initials: CH
authors.lastname: Wong
authors.forename: Pui Shan
authors.initials: PS
authors.lastname: Lo
authors.forename: Hu
authors.initials: H
authors.lastname: Zhu
authors.forename: Miu Ching
authors.initials: MC
authors.lastname: Lau
authors.forename: Man Yi
authors.initials: MY
authors.lastname: Chan
authors.forename: Lai Ling
authors.initials: LL
authors.lastname: Tsang
authors.forename: Yu Lin
authors.initials: YL
authors.lastname: Gou
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Chung
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D016900:Neurofilament Proteins; C051774:neurofilament protein H; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D010751:Phosphopyruvate Hydratase; D002118:Calcium