Enhancement of Rat MSC Capabilities by Intracelluar Release of Estradiol

Stem cell-based bone tissue engineering has emerged as an increasingly promising alternative approach for the treatment of craniofacial defects caused by congenital deficiencies, trauma, and dissection of tumors. Although bone marrow-derived MSCs are considered a potentially attractive cell source for this approach, the natural population of MSC is very limited and their differentiation capabilities are easily reduced following in vitro cell expansion. Thus, it is essential to develop strategies that can be used to improve the potential utilization of MSCs for clinical application. Estrogen effectively improves MSC capabilities and has strong potential as a regulator of MSCs. Our previous study has demonstrated that cationic modified poly (lactic-co-glycolic acid) (PLGA) particles can serve as a tool for intracellular delivery of estradiol (E2) to effectively execute estrogen regulation of  MSCs.

Objectives: This study is to evaluate in vitro and in vivo bone regenerative capability of MSCs with intracellular release of E2. 

Methods: After rat bone marrow MSCs took up E2-loaded PLGA  microparticles, their proliferation and in vitro osteogenic differentiation capabilities were measured using DNA quantification and real time PCR. In vivo bone regeneration of these MSCs was investigated using a rat calvarial bone defect model. 

Results: Rat MSCs with intracellular release of E2 delivered by PLGA microparticles exhibited significantly higher proliferation rate compared to the controls.  mRNA expression of osteocalcin, an osteogenic differentiation marker, of treated MSCs was significantly up-regulated compared to control groups after they were exposed to osteogenic differentiation medium in vitro. Bone regeneration at calvarial defects treated by MSCs with uptake of E2-loaded PLGA particles are faster than controls.  

Conclusions: Intracellular release of E2 delivered by PLGA microparticles effectively enhanced proliferation and bone regenerative capabilities of MSCs. This approach can be potentially used to improve the capabilities of MSCs for MSC-based bone tissue engineering.