Effect of Glyburide on Human Mesenchymal Stem Cell Development
Authors:
Thuy Bach, Justin D'Agostino, Yuanxiang ZhaoMentor:
Yuanxiang Zhao, Professor of Biological Sciences, California State Polytechnic University PomonaGlyburide is a commonly prescribed anti-diabetic medication that has been clinically linked to significant weight gain in patients, a phenomenon termed as obesogenic effect. However, the underlying mechanisms that cause drug induced weight gain are largely unknown. One of the potential cell targets of obesogenic drugs is human mesenchymal stem cells (hMSCs). These cells are important for maintaining adipose tissue homeostasis. The objective of our study is to examine the short-term and long-term effects of glyburide on human hMSCs survival, proliferation, and differentiation. hMSCs were treated short- (≤ 10 days) or long-term (≥ 30 days) with glyburide at two different concentrations (0.2 and 1 μM) within the range of its physiological levels detected in human body, or its corresponding solvent controls. Pretreated cells were then subjected to cell viability and differentiation assays and results are compared between glyburide and control treatment groups. At both 0.2 and 1 μM, glyburide significantly promoted osteogenic differentiation of hMSCs after either short- or long-term treatment. Adipogenic differentiation also trended higher (p≤ 0.1) in glyburide treated cells vs. control after long-term treatment. The tested concentrations however did not appear to have significant effects on either cell viability based on resazurin assay or cell cycle distribution based on flow cytometry cell cycle analysis, after both short- and long-term treatments. Our results indicate that glyburide could affect both adipogenic and osteogenic differentiation of hMSCs at physiological levels without affecting the cells’ viability or proliferation.