title: Neurogenic potential of progenitors derived from human circulating CD14+ monocytes.
abstract: We previously reported a primitive cell fraction derived from human circulating CD14+ monocytes, named monocyte-derived multipotential cells (MOMC), that can differentiate along mesenchymal lineages, including bone, cartilage, fat, skeletal muscle and cardiac muscle. In this study, we investigated whether MOMC can differentiate into the neuronal lineage. MOMC were fluorescently labelled and cocultivated with a primary culture of rat neurons for up to 4 weeks. The protein and gene expressions of neuron-specific markers in the human MOMC were evaluated over time using immunohistochemistry, in situ hybridization and reverse transcription followed by PCR. Shortly after cocultivation with rat neurons, nearly all the MOMC expressed early neuroectodermal markers, Mash1, Neurogenin2 and NeuroD, together with nestin, an intermediate filament expressed in neurogenesis. After 14 days of coculture, a subpopulation of MOMC displayed a multipolar morphology with elongated neurites and expressed mature neuron-specific markers, including neurofilament, microtubule-associated protein type 2, beta3-tubulin, NeuN and Hu. Transdifferentiation of monocytes into the neuroectodermal lineage was shown by the simultaneous expression of proneural markers and CD45/CD14 early in the differentiation process. The cocultivated MOMC retained their proliferative capacity for at least 16 days. Finally, the neuronal differentiation of MOMC was observed when they were cultured with neurons without cell-to-cell contact. The capacity of MOMC to differentiate into both mesodermal and neuroectodermal lineages suggests that circulating CD14+ monocytes are more multipotential than previously thought.
authors.affiliation: Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kodama
authors.forename: Takafumi
authors.initials: T
authors.lastname: Inoue
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Watanabe
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yasutomi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Masataka
authors.initials: M
authors.lastname: Kuwana
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D013997:Time Factors
chemical_list: D000943:Antigens, Differentiation; D018950:Lipopolysaccharide Receptors; D009419:Nerve Tissue Proteins