Simvastatin enhances proliferation and pluripotent gene expression by canine bone marrow-derived mesenchymal stem cells (cBM-MSCs) in vitro
Sirirat Nantavisai,
Watchareewan Rodprasert,
Koranis Pathanachai,
Parattakorn Wikran,
Podchana Kitcharoenthaworn,
Saritpakorn Smithiwong,
Suyakarn Archasappawat,
Chenphop Sawangmake
Affiliations
Sirirat Nantavisai
Veterinary Pharmacology and Stem Cell Research Laboratory, Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand; Special Task Force for Activating Research (STAR) in Biology of Embryo and Stem Cell Research in Veterinary Science, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
Watchareewan Rodprasert
Veterinary Pharmacology and Stem Cell Research Laboratory, Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand; Special Task Force for Activating Research (STAR) in Biology of Embryo and Stem Cell Research in Veterinary Science, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
Koranis Pathanachai
Veterinary Pharmacology and Stem Cell Research Laboratory, Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand; Special Task Force for Activating Research (STAR) in Biology of Embryo and Stem Cell Research in Veterinary Science, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
Parattakorn Wikran
Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
Podchana Kitcharoenthaworn
Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
Saritpakorn Smithiwong
Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
Suyakarn Archasappawat
Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand
Chenphop Sawangmake
Veterinary Pharmacology and Stem Cell Research Laboratory, Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand; Special Task Force for Activating Research (STAR) in Biology of Embryo and Stem Cell Research in Veterinary Science, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand; Corresponding author.
Establishing the intervention to enhance proliferation and differentiation potential is crucial for the clinical translation of stem cell-based therapy. In this study, the effects of simvastatin on these regards were explored. Canine bone marrow-derived mesenchymal stem cells (cBM-MSCs) were treated with 4 doses of simvastatin, 0.1, 1, 10, and 100 nM. Simvastatin in low-dose range, 0.1 and 1 nM, enhanced dose-dependent cell proliferation at day 5 and 7. Exploration of the mechanisms revealed that simvastatin in low-dose range dose-dependently upregulated sets of cell cycle regulators, Cyclin D1 and Cyclin D2; proliferation marker, Ki-67; and anti-apoptotic gene; Bcl-2. Interestingly, pluripotent markers, Rex1 and Oct4, were dramatically increased upon the low-dose treatment. Contrastingly, treatment with high-dose simvastatin suppressed the expression of those genes. Thus, the results suggested beneficial effects of simvastatin on cBM-MSCs proliferation and expansion. Further study regarding differentiation potential and underlying mechanisms will accelerate the clinical application of the molecule on veterinary stem cell-based therapy.
