title: Marrow stromal cells, mitosis, and neuronal differentiation: stem cell and precursor functions.
abstract: To define relationships among marrow stromal cells (MSCs), multipotential progenitors, committed precursors, and derived neurons, we examined differentiation, mitosis, and apoptosis in vitro. Neural induction medium morphologically converted over 70% of MSCs to typical neurons, which expressed tau, neuronal nuclear antigen, neuron-specific enolase, and TUC-4 within 24 hours. A subset decreased fibronectin expression, consistent with mesenchymal to neuroectodermal conversion. More than 35% of differentiating neurons incorporated bromodeoxyuridine (BrdU) and divided, increasing cell number by 60%, while another subpopulation differentiated without incorporating BrdU or dividing. Inhibition of mitosis and DNA synthesis did not prevent neural differentiation, with 70% of blocked cells expressing tau and displaying neuronal morphologies. By deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, less than 1% of cells underwent apoptosis at 36 and 72 hours, suggesting differentiation without cell-selective mechanisms. Apparently, MSCs may directly differentiate into neurons without passing through a mitotic stage, suggesting that distinctions among stem cells, progenitors, and precursors are more flexible than formerly recognized.
authors.affiliation: University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway 08854, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Muñoz-Elías
authors.forename: Dale
authors.initials: D
authors.lastname: Woodbury
authors.forename: Ira B
authors.initials: IB
authors.lastname: Black
mesh_terms: D000818:Animals; D017209:Apoptosis; D001710:Biotin / Q000737:chemistry; D001854:Bone Marrow Cells / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation; D004247:DNA / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008938:Mitosis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology*; D013997:Time Factors
chemical_list: D005353:Fibronectins; D001710:Biotin; D004247:DNA; D001973:Bromodeoxyuridine