Estrogen as a novel agent for induction of adipose-derived mesenchymal stem cells for osteogenic differentiation: in vivo bone tissue-engineering study.

Background: This study investigated whether the in vivo osteogenic differentiation potential of adipose-derived mesenchymal stem cells is enhanced by 17β-estradiol.

Methods: Thirty Sprague-Dawley rats were randomized and divided into five experimental groups. For the surgical procedure, biparietal full-thickness bone defects (7 mm in diameter) were created. A chitosan-hydroxyapatite scaffold was used as the vehicle system for 17β-estradiol-loaded nanoparticles and adipose-derived mesenchymal stem cells. The first group, the blank defect group, was the control group. The defects were filled with either scaffold, estradiol, and scaffold; scaffold and adipose-derived mesenchymal stem cells; or estradiol, scaffold, and adipose-derived mesenchymal stem cells as experimental groups. The rats were killed at the end of weeks 4 and 12, and their calvariae were harvested for histologic and microtomographic evaluation.

Results: Micro-computed tomographic evaluation of estradiol, scaffold, and adipose-derived mesenchymal stem cells revealed the highest median value (82.59 ± 17.17), and the difference was significant compared with the blank defect group (p = 0.004). Histologic samples demonstrated a significant difference between experimental groups for bone defect repair at the end of weeks 4 and 12 (p = 0.003 and p < 0.001). The estradiol, scaffold, and adipose-derived mesenchymal stem cell group had the highest median score (3.00 ± 0.0) at week 12, which was significantly higher than scores for the scaffold and adipose-derived mesenchymal stem cell group and the blank defect group.

Conclusion: 17β-Estradiol appears to be a novel and promising agent for future cell-based bone tissue-engineering studies.