骨髓间充质干细胞在微损伤环境中修复骨不连

Bone marrow mesenchymal stem cells for bone nonunion under micro-damage environment

背景:骨髓干细胞能够增殖再生,与传统的手术治疗方案结合能明显增强骨不连的治疗效果,具有重要的应用价值。目的:探讨骨髓间充质干细胞在微损伤环境中对骨不连的治疗效果。方法:选取清洁级纯种新西兰大白兔40只,采用随机数字表法分为实验组与对照组,每组20只。按照手术操作流程获取胫骨骨髓,分离培养骨髓间充质干细胞,待细胞增殖到第3代够107数量级时,进行超顺磁氧化铁纳米粒子培养标记。在兔前肢桡骨中段约15 mm处造成骨缺损,骨缺损6周发生骨不连。实验组大白兔将骨髓间充质干细胞与髂骨碎粒一起植入骨缺损处。对照组不进行干细胞移植,于骨缺损处植入髂骨碎粒。术后12周内,观察大白兔骨不连部位大体形态、X射线片、病理学染色结果。结果与结论:实验组术后明显发现骨痂,骨缺损处逐渐修复,直至完全愈合;对照组大白兔骨不连部位没有骨痂,骨髓腔封闭,充填肉芽组织。实验组有增生活跃的软骨组织,碎粒融合,骨缺损处出现类骨质,成骨细胞进行性增加;对照组软骨增生差,有大量死骨,骨粒未融合,没有成骨细胞。实验组桡骨缺损部位X射线显示云雾状影,骨髓腔恢复再通,骨骼塑形好;对照组骨碎粒吸收较少,骨髓腔部分闭塞,骨骼未连接,缺损处硬化。结果显示在局部微损伤环境中,骨髓间充质干细胞能够增殖分化为成骨细胞,修复骨缺损导致的骨不连具有显著效果。

BACKGROUND： Bone marrow stem cells combined with traditional surgery regimen can significantly improve the therapeutic effects on bone nonunion, which are considered to have an important application value. OBJECTIVE： To explore therapeutic effect of bone marrow mesenchymal stem cells on bone nonunion under micro-damage environment. METHODS： Forty New Zealand white rabbits were selected and randomized into experimental and control groups, 20 rabbits in each group. Bone marrow of the tibia was extracted to isolate and culture bone marrow mesenchymal stem cells. Passage 3 cells with the order of magnitudes of 107 were labeled by superparamagnetic iron oxide nanoparticles. A 15-mm bone defect was made at the middle of the radius of the rabbit forelimb. Bone nonunion appeared at 6 weeks after bone defects. Bone marrow mesenchymal stem cells combined with iliac particles were implanted into the bone defect of rabbits in the experimental group, and only iliac particles were implanted into the bone defect of rabbits in the control group. Within 12 weeks after implantation, the bone nonunion was observed through gross morphology, X-ray observation, and pathological observation. RESULTS AND CONCLUSION： After implantation, a remarkable callus was found in the experimental group, and the bone defect recovered gradually until it was completely healed; in the control group, there was no callus, and the bone marrow cavity was closed and full of granulation tissues. In the experimental group, there wereactively proliferated cartilage tissues, bone particles were fused, osteoid structures appeared, and osteoblasts proliferated progressively; in the control group, poor cartilage hyperplasia was found, and there were a large amount of dead bone tissues but no fused bone particles and osteoblasts. In the experimental group, X-ray films on the defected radium showed cloudiness-like shadow, the bone marrow cavity was recanalized, and the skeleton was shaped well; in the control group, few bone particles were absorbed, the bone marrow cavity was partly recanalized, and the injured bone was not healed with osteosclerosis. These findings indicate that under the micro-damage environment, bone marrow mesenchymal stem cells can differentiate into osteoblasts to repair bone defects-induced bone nonunion.