Valproic acid stimulates in vitro migration of the placenta-derived mesenchymal stem/stromal cell line CMSC29

Abstract

Background: The placenta is an abundant source of mesenchymal stem/stromal cells (MSC), but our understanding of their functional properties remains limited. We previously created a placental-derived chorionic MSC (CMSC) cell line to overcome the difficulties associated with conducting extensive ex vivo optimization and experimental work on primary cells. The aim of this study was to characterize the migratory behavior of the CMSC29 cell line in vitro. Methods: Stimulators of MSC migration, including two cytokines, stromal cell-derived factor-1α (SDF-1α) and hepatocyte growth factor (HGF), and a pharmacological agent, valproic acid (VPA), were tested for their ability to stimulate CMSC29 cell migration. Assessment of cell migration was performed using the xCELLigence Real-Time Cell Analyzer (RTCA). Results: There was no significant increase in CMSC29 cell migration towards serum free medium with increasing concentration gradients of SDF-1α or HGF. In contrast, treating CMSC29 cells with VPA alone significantly increased their migration towards serum free medium. Conclusions: Immortalized CMSC29 cells retain important properties of primary CMSC, but their migratory properties are altered. CMSC29 cells do not migrate in response to factors that reportedly stimulate primary MSC/CMSC migration. However, CMSC29 increase their migration in response to VPA treatment alone. Further studies are needed to determine the mechanism by which VPA acts alone to stimulate CMSC29 migration. Still, this study provides evidence that VPA pre-treatment may improve the benefits of cell-based therapies that employ certain MSC sub-types.

Comparison the effects of hypoxia-mimicking agents on migration-related signaling pathways in mesenchymal stem cells

“…*p \ 0.05; *p \ 0.01 and ****p \ 0.0001 were considered significant as compared to the untreated control and # was significant as compared to the other groups. VPA valproic acid, CoCl 2 cobalt chloride, DFX deferoxamine increase the in vitro migration of the cells (Al-Sowayan et al 2019). Similarly, in this study we observed that pre-treatment of Ad-MSC with VPA could increase the migratory behaviour of the cells.…”

Similar Population of CD133+ and DDX4+ VSEL-Like Stem Cells Sorted from Human Embryonic Stem Cell, Ovarian, and Ovarian Cancer Ascites Cell Cultures: The Real Embryonic Stem Cells?

“…In this study, valproic acid was used for the first time to activate VSEL-like stem cells in vitro from ovaries that are usually quiescent after sorting and are highly efficient. Some other studies showed that valproic acid, a fatty acid derivative, was efficient in ex vivo expansion of other types of stem cells, such as haematopoietic stem cells from umbilical cord blood [54] and placenta-derived mesenchymal/stromal stem cells [55]. Otherwise, it is an important FDA-approved drug component with several beneficial effects and of great interest for the treatment of different types of cancers [56].…”

Stem Cell Dynamics and Cytoceuticals for Therapeutics and Toxicity Screening: A Review

“…In an attempt to characterize migration in a placental-derived chorionic mesenchymal stem cell line, [61] discovered that valproic acid increased migration of the mesenchymal stem cell line. These authors also reported that mesenchymal stem cell migration was associated with adherence to and transmigration through endothelial barrier [62]. Again, mesenchymal stem cells as well as exosomes released from mesenchymal stem cell have been reported to be supportive in treatment of osteoarthritis [63].…”