Novel transplant of combined platelet-rich fibrin Releasate and bone marrow stem cells prevent bone loss in Ovariectomized osteoporotic mice

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 releasates (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 tested to investigate the accumulative effects of BMSCS and PRFr on bone quality. Eight weeks after 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 osteoporosis model 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 change to BMD and bone trabeculae could be detected in mice that received single-injection 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 spacing become narrower in OVX-mice treated with quadruple injection of BMSCs and combined PRFr and BMSCs than untreated control.

The Potential Therapeutic Effects of Platelet-Derived Biomaterials on Osteoporosis: A Comprehensive Review of Current Evidence

“…Several studies have demonstrated the effectiveness of platelet concentrates for the treatment and management of osteoporosis (Tables 2 and 3 ) [ 21 – 23 , 37 , 56 – 64 ]. All studies were conducted on ovariectomized (OVX) animal models including mice [ 22 , 23 , 37 , 56 ], rats [ 21 , 57 – 60 , 62 , 64 ], and rabbits [ 61 , 63 ]. In these studies, the systemic and localized application of platelet concentrates (PRP or PRF) alone or in combination with osteoinductive and osteoconductive biomaterials has been investigated [ 21 , 37 , 57 , 58 , 60 – 64 ].…”

“…Thus, the authors [ 23 ] concluded that the combined application of ADSCs and PRFr was the most optimized treatment for the healing of bone defects in these osteoporotic animals. In another study by Wong et al [ 22 ], PRFr was used in conjunction with bone marrow stem cells (BMSCs) and intravenously injected either once only or once a week for 4 consecutive weeks during the 8 week study period. PRFr alone and BMSCs alone were utilized as controls.…”

“…Based on the micro-CT analysis after 8 weeks, the only group which showed significant improvements in enhancing BMD and decreasing trabecular separation and spacing was the combined application of PRFr and BMSCs ( Figure 4 ) [ 22 ]. Both the PRFr + BMSCs and BMSCs alone groups significantly improved BV/TV while PRFr alone did not show any significant improvement which slightly contradicted the outcomes of Wong et al [ 22 , 23 ]. In their study, all groups demonstrated improvements in BV/TV following 4 weekly injections [ 22 ].…”

“…In their study, all groups demonstrated improvements in BV/TV following 4 weekly injections [ 22 ]. Although both Sheu et al [ 23 ] and Wong et al [ 22 ] performed relatively similar studies in terms of their protocols and the volume of the injection material, intervention time points, and time of sacrifice, the sole effect of PRFr was deemed more favorable in the study by Sheu et al [ 23 ]. One noted difference between the studies was the fact that the preparation of PRFr was different between the studies which may have affected the results.…”

“…One noted difference between the studies was the fact that the preparation of PRFr was different between the studies which may have affected the results. Interestingly, it was observed that IV injections of ADSCs yielded better outcomes when compared to BMSCs for the treatment of osteoporosis [ 22 , 23 ]; however, further clinical studies would be required to appraise these findings.…”