title: Valproic acid promotes neuronal differentiation by induction of neuroprogenitors in human bone-marrow mesenchymal stromal cells.
abstract: Recent studies have shown that the inhibition of histone deacetylases (HDACs) induces the differentiation of diverse cancer and stem cells, which suggests HDAC inhibitors may be good candidates for the induction of stem cell differentiation. In this study, we investigated the effects of a HDAC inhibitor, valproic acid (VPA), for the neuronal differentiation of human bone marrow-mesenchymal stromal cells (hBM-MSCs). VPA-treated MSCs had significant increases in their expression of the neuro-progenitor marker Nestin, Musashi, CD133, and GFAP, as measured by real-time PCR and immunoblot analysis. When VPA-pretreated MSCs were differentiated with neuronal induction media (VPA-dMSCs), they exhibited a cell body and dendritic morphology similar to neurons. The number and neurite length of these VPA-dMSCs significantly increased compared to differentiated MSCs (dMSCs). The VPA-dMSCs and dMSCs had significantly increased transcripts of neuronal-specific marker genes, including Nestin, Musashi, CD133, GFAP, NeuN, MAP-2, NF-M, KCNH1, and KCNH5. The cells also showed a higher expression of the neuronal marker proteins Nestin and NF-M from immunocytochemical staining and immunoblot analysis. This study has shown that VPA pretreatment of hBM-MSCs, following their incubation with neuronal induction media, effectively stimulates neuronal cell differentiation to BM-MSCs.
authors.affiliation: Department of Biology, College of Natural Sciences, Chosun University, GwangJu 501-759, Republic of Korea.
authors.forename: Sin-Gu
authors.initials: SG
authors.lastname: Jeong
authors.forename: Takbum
authors.initials: T
authors.lastname: Ohn
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Goang-Won
authors.initials: GW
authors.lastname: Cho
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D003712:Dendrites / Q000648:ultrastructure; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid
keywords: BHA; BM-MSCs; Bone marrow-mesenchymal stem cells (BM-MSCs); CNS; FBS; HDAC; HSC; Histone deacetylase (HDAC); MSCs; Mesenchymal stem cells (MSCs); Neuronal differentiation; PBS; PCR; ROS; RT; VPA; Valproic acid (VPA); bone marrow-mesenchymal stromal cells; butylated hydroxyanisole; central nervous system; fetal bovine serum; hematopoietic stem cells; histone deacetylase; mesenchymal stromal cells; phosphate-buffered saline; polymerase chain reaction; reactive oxygen species; room temperature; valproic acid