Wong Chin-Chean, Liao Jeng-Hao, Sheu Shi-Yuan, Lin Po-Yu, Chen Chih-Hwa, Kuo Tzong-Fu
Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.
Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
BMC Musculoskelet Disord. 2020 Aug 8;21(1):527. doi: 10.1186/s12891-020-03549-y.
Osteoporosis is a metabolic bone disorder characterized by deterioration in the quantity and quality of bone tissue, with a consequent increase susceptibility to fracture.
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.
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 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.
骨质疏松症是一种代谢性骨病，其特征是骨组织的数量和质量下降，从而导致骨折易感性增加。
在本研究中，我们试图确定富含血小板纤维蛋白释放物（PRFr）在增强基于干细胞的疗法治疗骨质疏松性骨病的疗效方面的作用。通过对12周龄雌性ICR（癌症研究所）小鼠进行双侧卵巢切除术建立骨质疏松小鼠模型。术后8周，对去卵巢（OVX）小鼠不进行治疗（对照组）或注射PRFr、骨髓干细胞（BMSCs）或BMSCs与PRFr的组合。测试了两种不同的注射（单次与四次）剂量，以研究BMSCS和PRFr对骨质量的累积影响。注射8周后，分析胫骨微观结构轮廓的变化，包括骨体积与总组织体积的百分比（BV/TV，%）、骨矿物质密度（BMD，g/cm³）、小梁数量（Tb.N，个/mm）和小梁间距（Tb.Sp，mm）以及骨组织学。
OVX小鼠成功建立了绝经后骨质疏松模型，表现为骨密度降低、BV/TV降低、Tb.N降低但Tb.Sp增加。注射8周后，接受单次注射方案的小鼠骨密度无明显变化，未检测到骨小梁。相比之下，接受4剂PRFr和BMSCs联合治疗的小鼠，与未治疗的OVX小鼠相比，骨密度、BV/TV和TB.N增加，TB.Sp显著降低。此外，组织学分析显示，接受四次注射BMSCs以及联合PRFr和BMSCs治疗的OVX小鼠的小梁间距比未治疗的对照组变窄。
全身给予BMSCs和PRFr联合治疗可防止OVX诱导的小鼠骨质流失。此外，四次注射组的骨轮廓评分改善优于单次注射组，可能是通过增加细胞和生长因子的效应大小。我们的数据还表明，BMSCs和PRFr联合治疗在增强成骨方面具有更好的效果，这可能为开发一种新的骨质疏松症治疗策略提供思路。
