Bone morphogenetic protein-2 in biodegradable gelatin and β-tricalcium phosphate sponges enhances the in vivo bone-forming capability of bone marrow mesenchymal stem cells
Bone morphogenetic protein-2 in biodegradable gelatin and β-tricalcium phosphate sponges enhances the in vivo bone-forming capability of bone marrow mesenchymal stem cells
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DOI：
10.1002/term.427
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发表时间：
2012-04-01
影响因子：
3.3
通讯作者：
Ohgushi, Hajime
中科院分区：
文献类型：
--
作者：
Tadokoro, Mika;Matsushima, Asako;Ohgushi, Hajime
骨髓间充质干细胞（MSCs）因其向成骨细胞分化的能力而被用于骨组织工程，但其应用存在争议。为了提高它们的能力，我们制备了可生物降解的明胶海绵纳入β-磷酸三钙陶瓷（GT海绵），这已被证明具有良好的药物控制释放性能。以骨形态发生蛋白-2（BMP-2）和骨髓间充质干细胞（MSCs）为载体，将4种不同的骨形态发生蛋白复合物（BMP-MSCGT、BMP-MSCGT和BMP-MSCGT）植入大鼠皮下，观察其成骨分化情况。植入后两周，组织学切片显示BMPGT周围部分和BMPMSCGT植入物的几乎全部体积中有新骨形成。4周后，组织学和microCT分析显示BMPMSCGT植入物中有广泛的骨形成。碱性磷酸酶和骨特异性骨钙素的基因表达和生化分析证实了组织学结果。这些结果表明，骨髓间充质干细胞，GT和BMP的组合协同增强成骨能力，并提供了合理的基础上，其在骨重建的临床应用。版权所有（c）2011约翰威利父子有限公司
Bone marrow mesenchymal stem cells (MSCs) have been used for bone tissue engineering due to their osteogenic differentiation capability, but their application is controversial. To enhance their capability, we prepared biodegradable gelatin sponges incorporating beta-tricalcium phosphate ceramics (GT sponge), which has been shown to possess excellent controlled drug-release properties. The GT sponge was used as a carrier for both rat MSCs and bone morphogenetic protein-2 (BMP-2) and osteogenic differentiation was assessed by subcutaneous implantation of four different kinds of implants, i.e. GT-alone, MSCGT composites, BMPGT composites and BMPGT composites supplemented with MSCs (BMPMSCGT) in rats. Two weeks after implantation, histological sections showed new bone formation in the peripheral parts of the BMPGT and in almost the total volume of the BMPMSCGT implants. After 4 weeks, histology as well as microCT analyses demonstrated extensive bone formation in BMPMSCGT implants. Gene expression and biochemical analyses of both alkaline phosphatase and bone-specific osteocalcin confirmed the histological findings. These results indicate that the combination of MSCs, GT and BMP synergistically enhances osteogenic capability and provides a rational basis for their clinical application in bone reconstruction. Copyright (c) 2011 John Wiley & Sons, Ltd.