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.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 better effect in enhancing osteogenesis, which may provide insight for the development of a novel therapeutic strategy in osteoporosis treatment.

Analysis of type I osteoporosis animal models using synchrotron radiation

“…There was a difference in staining of tibia microstructures in the comparison of (a) OVX and (b) SHAM. During the staining process, the same reaction as in previous studies could be confirmed (Wong et al, 2020). We were also able to acquire a twodimensional (2D) image of a limited location and the bone was found to be made of hard tissue.…”

Evaluation of the Efficacy of Stem Cell Therapy in Ovariectomized Osteoporotic Rats Based on Micro-CT and Dual-Energy X-Ray Absorptiometry: A Systematic Review and Meta-Analysis

“…Elseweidy et al [26] demonstrated that the combination of MSC and the antioxidant resveratrol was more effective in increasing bone mass and improving osteoporosis than treatment alone. Some studies had shown that the combination of plateletrich fibrin releasates (PRFr) and BMSCs [27] or ADSCs 10 Stem Cells International [28] could reduce bone loss in OVX osteoporotic mice. Based on the above findings, we can find that stem cell transplantation holds promise as a potential treatment for osteoporosis.…”

The Evidence-based Effect of Platelet-rich Fibrin in Osteogenesis: A Systematic Review and Meta-analysis

“…Moreover, red i-PRF combined with bone substitute material application may be more effective than the yellow i-PRF [12]. Intervention using the combination of BMSCs and PRFr has more significant results in improving osteogenesis, which served as an understanding for further developing a novel therapeutic strategy in treating osteoporosis [13]. Gold nanoparticles to the advanced PRF and fibrin and platelet byproducts could be new substitute strategies to enhance the osteogenesis capacity of the stem cells [14].…”