基因修饰干细胞治疗骨质疏松:临床前研究的Meta分析  

Gene-modified stem cells therapy for osteoporosis:a meta-analysis of preclinical studies

作　　者：向倩如 邓学健 陈华锋 梁嘉敏 安敏 杨力[1,2] Xiang Qianru;Deng Xuejian;Chen Huafeng;Liang Jiamin;An Min;Yang Li(Department of Endocrinology and Metabolism,Zhujiang Hospital,Southern Medical University,Guangzhou 510220,Guangdong Province,China;Department of Nutrition,Zhujiang Hospital,Southern Medical University,Guangzhou 510220,Guangdong Province,China)

机构地区：[1]南方医科大学珠江医院内分泌代谢科,广东省广州市510220 [2]南方医科大学珠江医院营养科,广东省广州市510220

出　　处：《中国组织工程研究》2022年第31期5053-5061,共9页Chinese Journal of Tissue Engineering Research

基　　金：广东省自然科学基金(2014A030310036,2018A030313609),项目负责人:杨力;南方医科大学临床研究育苗项目(LC2016YM007),项目负责人:杨力。

摘　　要：目的:基因修饰干细胞是骨质疏松的潜在疗法,处于临床前研究阶段,其疗效仍有争议。文章通过Meta分析基因修饰干细胞对骨质疏松动物的骨组织形态计量学指标和钙磷代谢指标的影响,评价其较单纯干细胞治疗骨质疏松的效果。方法:计算机检索PubMed、MEDLINE、Web of Science、中国知网和万方数据库建库至2021年6月关于基因修饰干细胞治疗骨质疏松动物的相关研究,采用R4.1.0软件进行Meta分析。主要结局指标为骨密度和骨体积分数,次要结局指标为骨小梁数量、骨小梁厚度、骨小梁分离度、血磷、血钙和血骨碱性磷酸酶。结果:共纳入22项动物实验研究。Meta分析结果示:①基因修饰干细胞(实验组)较单纯干细胞(对照组)增加骨质疏松动物的骨密度(SMD=2.23,95%CI:1.34-3.11,P<0.01)、骨体积分数(SMD=1.95,95%CI:1.07-2.83,P<0.01)、骨小梁数量(SMD=2.33,95%CI:1.34-3.32,P<0.01)、骨小梁厚度(SMD=1.47,95%CI:0.70-2.24,P<0.01)和血磷水平(MD=0.10,95%CI:0.08-0.12,P=0.08);②实验组的骨小梁分离度(SMD=-2.77,95%CI:-4.17至-1.36,P<0.01)、血钙水平(MD=-0.04,95%CI:-0.06至-0.03,P=0.82)和血骨碱性磷酸酶水平(MD=-4.46,95%CI:-5.12至-3.80,P=0.96)小于对照组。结论:相较于单纯干细胞,正向的基因修饰干细胞对骨质疏松动物的骨密度、骨质量和钙磷代谢有明显的改善作用。因纳入文献质量有限,以上结论需更多高质量大样本实验以补充验证。OBJECTIVE:Gene-modified stem cells therapy in osteoporosis is a promising method with controversy.This article analyzed the effects of gene-modified stem cells on bone histometrology and calcium phosphorus metabolism in osteoporosis animals by meta-analysis,and evaluated its efficacy compared with simple stem cells.METHODS:PubMed,MEDLINE,Web of Science,CNKI,and Wanfang databases were used to collect articles about gene-modified stem cells therapy in osteoporosis animals before June,2021.R4.1.0 software was used for meta-analysis.The primary outcome measures were bone mineral density and trabecular bone volume(BV/TV).The secondary outcome measures were trabecular number(Tb.N),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),blood phosphorus,blood calcium,and blood bone alkaline phosphatase.RESULTS:Totally 22 articles of animal experiments were included.The meta-analysis results showed:(1)gene-modified stem cells of the experimental group increased bone mineral density(SMD=2.23,95%CI:1.34-3.11,P<0.01),BV/TV(SMD=1.95,95%CI:1.07-2.83,P<0.01),Tb.N(SMD=2.33,95%CI:1.34-3.32,P<0.01),Tb.Th(SMD=1.47,95%CI:0.70-2.24,P<0.01)and blood phosphorus(MD=0.10,95%CI:0.08-0.12,P=0.08)in simple stem cells of the control group.(2)Tb.Sp(SMD=-2.77,95%CI:-4.17 to-1.36,P<0.01),blood calcium(MD=-0.04,95%CI:-0.06 to-0.03,P=0.82),and blood bone alkaline phosphatase(MD=-4.46,95%CI:-5.12 to-3.80,P=0.96)of the experimental group were lower than those in the control group.CONCLUSION:Compared with simple stem cells,positive gene-modified stem cells improve bone mineral density,bone quality,and calcium phosphorus metabolism in osteoporosis.Due to the included literature’s insufficient quality,higher quality and more random control trials are required to supplement the argument.

关 键 词：干细胞 骨质疏松 基因修饰 META分析 动物 实验 临床前研究 骨密度 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学]