Effects of valproic acid on the expression of trophic factors in human bone marrow mesenchymal stromal cells

• Published in: Neuroscience letters Vol. 526; no. 2; pp. 100 - 105
• Main Authors: Cho, Goang-Won, Kang, Byung Yong, Kim, Kyung-Suk, Kim, Seung Hyun
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 27.09.2012
• Subjects: Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bone marrow mesenchymal stromal cells (BM-MSCs); Cell Proliferation - drug effects; Cells, Cultured; Chemotaxis - drug effects; Humans; Indexing in process; Intercellular Signaling Peptides and Proteins - metabolism; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Migration; Neuroprotective Agents - pharmacology; Oxidative Stress - drug effects; Protection; Trophic factors; Valproic acid (VPA); Valproic Acid - pharmacology; PBS; BM-MSCs; VPA; Migration; FACS; Bone marrow mesenchymal stromal cells (BM-MSCs); MTT; Valproic acid (VPA); FBS; RT-PCR; Trophic factors; Protection; ELISA
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2012.08.015

► Various trophic factors are significantly increased in valproate-treated hBM-MSCs (VPA-MSCs). ► VPA-MSCs showed increased protective effects against oxidative stress. ► VPA-MSCs showed increased migratory ability. ► It suggests that VPA may be a candidate for the improvement of stem cells as trophic mediator. The potential of human bone marrow-mesenchymal stromal cells (hBM-MSCs) to differentiate into diverse cell types and secrete a variety of trophic factors makes them an excellent cell therapy tool for intractable diseases. However, their therapeutic efficacy has not yet been satisfied in preclinical and/or clinical trials with autologous or allogenic stem cells. To improve the efficacy of stem cell therapy, optimized conditions for stem cells need to be defined. In this study, we evaluated the effects of valproic acid (VPA), an HDAC inhibitor, in human BM-MSCs and assessed the expression of trophic factors (ANG, BDNF, ECGF1, bFGF-2, GDNF, HGF, IGF-1, PIGF, TGF-β1, and β-Pix) in MSCs treated with 200μg/ml VPA for 12h. Under these conditions the features of MSCs were not changed. The VPA-treated MSCs also showed an increased cell protective effect against oxidative injuries in MTT assays and improved migratory ability when examined by the Boyden chamber assay. This suggests that MSCs may be improved by treatment with an optimal VPA dose and incubation time, which may increase the efficacy of stem cell therapy.