Liao Yun, Zhang Xiao-Long, Li Ling, Shen Fu-Ming, Zhong Ming-Kang
Department of Clinical Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
Br J Clin Pharmacol. 2014 Oct;78(4):718-26. doi: 10.1111/bcp.12382.
Injury to bone is a significant clinical challenge, due to its limited regenerative capacity. The current methods of repairing bone defect are surgical, highly invasive and not always successful. A systematic review and meta-analysis of preclinical studies involving large animals with bone defects were conducted to determine the treatment outcomes with stem cell therapies.
A random effects meta-analysis of the available studies was conducted to assess the treatment outcomes including the rate of new bone formation and new bone mineral density (BMD). Stratified analyses were also conducted by separating studies based on each characteristic independently.
Pooled analysis of 20 preclinical studies showed a significant beneficial effect of stem cell therapy in increasing new bone formation (17.79%, 95% confidence interval [CI], 10.54, 25.03; P < 0.001) and BMD (276.94 mg cm(-2) , 95% CI, 62.71, 491.17; P < 0.001) for disease amelioration. Regarding new bone formation, a statistical improvement was similarly detected from randomized controlled trial groups (17.06%, 95% CI, 8.87, 25.24; P < 0.001) and cohort groups (17.43%, 95% CI, 10.79, 24.07; P < 0.001). Exploratory stratified analysis yielded significant predictors of new bone formation including cell number (<10(7) vs. ≥10(7) ; P = 0.048) and the route of cell delivery (combining with matrix scaffold showed more effect than direct cell injection, P = 0.041). The effect of stem cell therapy diminished after 12 weeks.
The study results suggest that stem cell therapy improves new bone formation and BMD in bone defect models. Future trials should focus on the transplantation of ≥10(7) stem cells, especially using slow release biodegradable scaffolds or repetitive cell injections.
由于骨的再生能力有限，骨损伤是一项重大的临床挑战。目前修复骨缺损的方法是手术治疗，具有高度侵入性且并非总是成功。我们对涉及患有骨缺损的大型动物的临床前研究进行了系统评价和荟萃分析，以确定干细胞疗法的治疗效果。
对现有研究进行随机效应荟萃分析，以评估包括新骨形成率和新骨矿物质密度（BMD）在内的治疗效果。还根据每个特征独立地对研究进行分层分析。
对20项临床前研究的汇总分析表明，干细胞疗法在增加新骨形成（17.79%，95%置信区间[CI]，10.54，25.03；P<0.001）和骨密度（276.94mg/cm²，95%CI，62.71，491.17；P<0.001）以改善病情方面具有显著的有益效果。关于新骨形成，在随机对照试验组（17.06%，95%CI，8.87，25.24；P<0.001）和队列组（17.43%，95%CI，10.79，24.07；P<0.001）中同样检测到统计学上的改善。探索性分层分析得出了新骨形成的显著预测因素，包括细胞数量（<10⁷与≥10⁷；P = 0.048）和细胞递送途径（与基质支架联合显示比直接细胞注射效果更好，P = 0.041）。12周后干细胞疗法的效果减弱。
研究结果表明，干细胞疗法可改善骨缺损模型中的新骨形成和骨密度。未来的试验应侧重于移植≥10⁷个干细胞，尤其是使用缓释可生物降解支架或重复细胞注射。
