Angiogenesis and Osteogenesis Mesenchymal Stem Cell Sheet with Activated Platelet-Rich Plasma Enhances Fracture Healing in a Rat Tibia Model
Angiogenesis and Osteogenesis Mesenchymal Stem Cell Sheet with Activated Platelet-Rich Plasma Enhances Fracture Healing in a Rat Tibia Model
复制标题
血管生成和成骨间充质干细胞片与活化的富含血小板血浆可增强大鼠胫骨模型的骨折愈合
DOI：
10.1166/jbt.2019.1945
复制
发表时间：
2019
影响因子：
0.1
通讯作者：
Feng Gang
中科院分区：
文献类型：
--
作者：
Qi Yiying;Zhang Yuxiang;Feng Gang
目的骨折不愈合是临床常见的问题。在本报告中，我们通过使用血管生成和成骨间充质干细胞（MSC）片和活化的富血小板血浆（PRP）来增强骨愈合。方法体外研究活化PRP刺激大鼠骨髓间充质干细胞和辛伐他汀和活化PRP刺激的MSC片的成骨分化。我们进一步研究了骨髓间充质干细胞片、PRP或骨髓间充质干细胞片和PRP处理的骨折大鼠胫骨的体内成骨情况。在第2周和第8周进行x线，显微计算机断层扫描和组织学分析。结果经活化PRP处理后的MSCs， salizarin red染色定量和碱性磷酸酶定量显示其成骨潜能。碱性磷酸酶、骨钙素、骨保护素和血管内皮生长因子在辛伐他汀处理的MSCs或活化的prp诱导的MSC片中的表达水平显著高于未诱导的MSC片，表明血管生成和成骨发生了。x线、显微计算机断层摄影和组织学切片显示，MSC薄片/PRP移植组骨折部位周围形成了骨痂。MSC薄片/PRP组在8周时实现骨愈合。结论活化PRP移植间充质干细胞片可使模型骨折完全愈合。血管生成和成骨间充质干细胞片局部应用活化PRP可用于治疗骨折，延迟骨愈合或不愈合的临床应用。
PurposeNonunion of fractured bones is a common clinical problem. In this report, we enhanced bone union by using angiogenic and osteogenic mesenchymal stem cell (MSC) sheets and activated platelet-rich plasma (PRP).MethodsThe osteogenic differentiation of rat bone marrow-derived MSCs stimulated with activated PRP and MSC sheets stimulated with simvastatin and activated PRP were investigated in vitro. We further investigated osteogenesis in vivo in fractured rat tibias treated with MSC sheets, PRP, or MSC sheets and PRP. X-ray, micro-computed tomography, and histological analysis were performed at 2 and 8 weeks.ResultsAlizarin red staining and quantification and alkaline phosphatase quantification showed the osteogenic potential of MSCs treated with activated PRP. The expression levels of alkaline phosphatase, osteocalcin, osteoprotegerin, and vascular endothelial growth factor in MSCs treated with simvastatin or in activated PRP-induced MSC sheets were significantly higher than those in non-induced MSC sheets, suggesting that angiogenesis and osteogenesis occurred. X-ray and micro-computed tomography photographs and histological sections showed callus formation around the fracture sites in the MSC sheet/PRP transplanted group. Bone union was achieved in the MSC sheet/PRP group at 8 weeks.ConclusionsOur results indicate that the fractures in our model were completely cured by transplanting MSC sheets with activated PRP. Angiogenic and osteogenic MSC sheets with locally applied activated PRP may have clinical use in the treatment of fractures, delayed bone union, or nonunion.