Methods: The proliferation, differentiation and telomere length of human MSCs were evaluated after blocking the activity of endogenous GCs using GR siRNA delivered by biodegradable poly (lactic-co-glycolic acid) (PLGA) microparticles.
Results: The results show that PLGA microparticles can serve as a delivery system of GR siRNA and maintain release of siRNA up to 40 days in vitro. Transfection of GR siRNA significantly down-regulates GR and up-regulates the expression of FGF-2 and Sox-11 of human MSCs. MSCs that have proliferated with endogenous GCs blocked in vitro have enhanced proliferation and telomere length and exhibit up-regulated expression of osteogenic markers under differentiation stimulation. Under adipogenic differentiation, MSCs proliferated in vitro with siRNA transfection resulting in significantly lower adipogenic markers compared to controls.
Conclusions: PLGA particles can serve as a tool for delivery of GR siRNA to effectively block the effects of endogenous GCs on MSCs, which has the potential to improve the capabilities of human MSCs for clinical application by preventing replicative senescence.
Keywords: Growth & development, Hormones and growth factors, Polymers and Tissue engineering