Adipose Derived Stem Cells Conditioned Media in Combination with Bioceramic-Collagen Scaffolds Improved Calvarial Bone Healing in Hypothyroid Rats

Background: Tissue engineering is an available treatment for large bone defects. The therapeutic effects of mesenchymal stem cell (MSC) are mostly attributed to secretion of many cytokines and growth factors. Many factors of MSC secretions accumulate in a conditioned medium and these factors recruit native cells into a defect site to generate new bone tissues. Objectives: The aim of this study was to evaluate the influence of adipose tissue derived MSCs-conditioned medium (ADMSC-CM) on bone repair of rats with critical-size calvarial defect. Methods: This experimental study was performed at Shahid Beheshti University of Medical Sciences, Tehran, Iran, from 2016 to 2017. Conditioned medium was collected from healthy rat adipose tissue derived MSC (ADMSC) at passage four. Calvarial bone defect was created in hypothyroid rats using a dental bur. Sampling was taken by the linear-mono-gram method to determine sample size (n = 6 per group). The rats were divided randomly into four groups based on graft material as follows: empty defect, scaffold (Bio-Oss/type I collagen gel), scaffold/ADMSCs, scaffold/ADMSC-CM. Evaluations weremadeat 4 and 8 weeks after surgery using stereological analysis. Results: Histological analysis at 8 weeks indicated that the newly regenerated tissue almost covered the defect in the ADMSC-CM group. Stereological analysis showed that ADMSC-CM increased regenerated bone and numbers of osteocytes and osteoblasts compared with the defect and scaffold groups (P < 0.05). Also, bone regeneration was more effective in animals treated with ADMSC-CM than in those received ADMSC. Conclusions: These results suggest an important role for ADMSC-CM in bone regeneration, through trophic impact of its cytokines andgrowthfactors that induce native cell proliferation and migration into the defect. Thus, ADMSC-CM seems to have good potential for application in bone tissue regeneration, in the cases of hypothyroidism.