联合应用基质细胞衍生因子1、辛伐他汀及骨胶原支架进行体内异位成骨

摘要/Abstract

摘要： 目的：探讨使用小鼠基质细胞衍生因子1（murine stromal cell-derived factor 1， mSDF-1）结合辛伐他汀（simvastatin，SIM）以及骨胶原支架（Bio-Oss^®）构建无外加种子细胞的组织工程化骨的可行性，并检验其体内异位成骨的效果。方法：将32只ICR小鼠随机分为4组,每组8只，于小鼠颅部做皮肤切口，各组小鼠分别植入：(1)1 ∶50（体积比）的二甲基亚砜（dimethyl sulfoxide，DMSO）/磷酸盐缓冲液（phosphatebuffered saline，PBS）混合液+骨胶原支架（空白对照组）；(2)10^-3 mol/L SIM溶液+骨胶原支架（SIM组）；(3)200 mg/L mSDF-1溶液+骨胶原支架（mSDF-1组）；(4)10^-3 mol/L SIM+200 mg/L mSDF-1溶液+骨胶原支架（SIM+mSDF-1组）。植入1周后，连续2 d，每天分别在支架局部注射上述各组相应的溶液50 μL。饲养6周后，取出支架及其周围组织，通过软X射线投射成像及灰度测定、HE染色、免疫组织化学染色的方法，定性及定量观察其成骨效果。结果：SIM+mSDF-1组软X射线灰度值［（421 836.5±65 425.7）像素］明显高于空白对照组［（153 345.6±45 222.2）像素，P<0.01］、SIM组［（158 119.2±100 284.2）像素，P<0.01］以及mSDF-1组［（255 529.5±152 142.4）像素，P<0.05］；在SIM+mSDF-1组内可见明显的骨桥蛋白和骨钙素的表达；SIM+mSDF-1组血管丛密度［（46±8）条/mm²］明显高于空白对照组［（23±7）条/mm², P<0.01］和SIM组［（24±6）条/mm², P<0.01］。结论：使用mSDF-1结合SIM以及骨胶原支架构建的无外加种子细胞的组织工程化骨可于小鼠颅部皮下异位成骨。

关键词: 趋化因子CXCL12, 辛伐他汀, 胶原, 骨生成

Abstract: Objective: To construct and evaluate a novel tissue-engineered bone composed of murine stromal cell-derived factor 1(mSDF-1), simvastatin (SIM) and collagen scaffold （Bio-Oss^®）, serving as a cell-homing approach for bone formation. Methods: In the study, 32 ICR mice were randomly divided into 4 groups，each group including 8 mice. The drug-loaded collagen scaffolds were implanted subcutaneously onto the cranium of each mouse according to the groups: (1) 1 ∶50 (volume ratio) dimethyl sulfoxide (DMSO) / phosphate-buffered saline(PBS) solution + collagen scaffold (blank control group); (2) 10^-3 mol/L SIM solution + collagen scaffold (SIM group); (3) 200 mg/L mSDF-1solution + collagen scaffold (mSDF-1 group); and (4) 10^-3 mol/L SIM +200 mg/L mSDF-1 solution + collagen scaffold (SIM + mSDF-1 group). One week after implantation, the mice were treated by injecting the same drug solution mentioned above around the scaffold once a day for two days. The specimens were harvested 6 weeks after implantation and the bone formation was evaluated by soft X-ray analysis, HE staining and immunohistochemical staining. Angiogenesis of each group was checked by calculation of vessels in each tissue section. Results: Six weeks after implantation, the collagen scaffolds were retrieved. The value of gray scale for the SIM+mSDF-1 group［（421 836.5±65 425.7）pixels］ was significantly higher than that of the blank control group［（153 345.6±45 222.2）pixels, P<0.01］, the SIM group ［（158 119.2±100 284.2）pixels, P<0.01］, and the mSDF-1 group［（255 529.5±152 142.4）pixels, P<0.05］; HE staining analysis revealed that significant bone formation was achieved in the SIM + mSDF-1 group; The immunohistochemical staining showed the existence of osteopontin and osteocalcin in the SIM + mSDF-1 group; There were more vessels in the SIM+mSDF-1 group［（46±8）vessels/mm²］ than in the blank control group ［(23±7) vessels/mm², P<0.01］, and the SIM group［(24±6) vessels/mm², P<0.01］. Conclusion: The novel tissue-engineered bone composed of mSDF-1, SIM and collagen scaffolds has the potential to form bone subcutaneously in vivo. It represents a novel method of in vivo bone regeneration without seed cell delivery.

Key words: Chemokine CXCL12, Simvastatin, Collagen, Osteogenesis

欧蒙恩, 张晓, 刘云松, 葛严军, 周永胜. 联合应用基质细胞衍生因子1、辛伐他汀及骨胶原支架进行体内异位成骨[J]. 北京大学学报（医学版）, 2015, 47(1): 47-51.

欧Meng-恩 , ZHANG Xiao, LIU Yun-Song, GE Yan-Jun, ZHOU Yong-Sheng. Ectopic osteogenesis of stromal cell-derived factor 1 combined with simvastatin loaded collagen scaffold in vivo[J]. Journal of Peking University(Health Sciences), 2015, 47(1): 47-51.

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