Synergistic Effect of Platelet-rich Fibrin Releasate and Bone Marrow Stem Cells in Preventing Bone Loss in Ovariectomized Mouse

Abstract

Background:Osteoporosis is a metabolic bone disorder characterized by deterioration in the quantity and quality of bone tissue, with a consequent increase susceptibility to fracture.Methods: In this study, we sought to determine the efficacy of platelet-rich fibrin releasate (PRFr) in augmenting the therapeutic effects of stem cell-based therapy in treating osteoporotic bone disorder. An osteoporosis mouse model was established through bilateral ovariectomy on 12 week-old female ICR (Institute of Cancer Research) mice. Eight weeks postoperatively, the ovariectomized(OVX) mice were left untreated (control) or injected with PRFr, bone marrow stem cells (BMSCs), or the combination of BMSCs and PRFr. Two different injection (single versus quadruple)dosages were testedto investigate the accumulative effects of BMSCS and PRFr on bone quality. Eightweeksafter injection, the changes in tibial microstructural profiles included the percentage of bone volume versus total tissue volume (BV/TV, %), bone mineral density (BMD, g/cm3), trabecular number (Tb.N, number/mm), and trabecular separation (Tb.Sp, mm) and bony histology were analyzed. Results: Postmenopausal osteoporosismodel was successfully established in OVX mice, evidenced by reduced BMD, decreased BV/TV, lower Tb.N but increased Tb.Sp..Eight weeks after injection, there was no significant changes to BMD and bone trabeculae could be detected in mice that received low-dose regimen. In contrast, in mice which received 4 doses of combined PRFr and BMSCs, the BMD, BV/TV, and TB.N increased, and the TB.Sp decreased significantly compared to untreated OVX mice. Moreover, the histological analysis showed the trabecular spacingbecome narrower in OVX-mice treated with high-dose injection of BMSCs and combined PRFr and BMSCs than untreated control.Conclusion: The systemic administration of combined BMSCs and PRFr protected against OVX-induced bone mass loss in mice. Moreover, the improvement of bony profile scores in quadruple injection group is better than the single-injection group, probably through the increase in effect size of cells and growth factors. Our data also revealed the combination therapy of BMSCs and PRFr has a synergistic effect in enhancing osteogenesis, which may provide insight for the development of a novel therapeutic strategy in osteoporosis treatment.