Chinese Journal of Tissue Engineering Research ›› 2022, Vol. 26 ›› Issue (31): 5053-5061.doi: 10.12307/2022.734
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Xiang Qianru1, Deng Xuejian1, Chen Huafeng1, Liang Jiamin1, An Min1, Yang Li1, 2
Received:
2021-10-25
Accepted:
2021-11-23
Online:
2022-11-08
Published:
2022-04-25
Contact:
Yang Li, MD, Master’s supervisor, Associate professor, Associate chief physician, Department of Endocrinology and Metabolism, and Department of Nutrition, Zhujiang Hospital, Southern Medical University, Guangzhou 510220, Guangdong Province, China
About author:
Xiang Qianru, Master candidate, Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou 510220, Guangdong Province, China
Supported by:
CLC Number:
Xiang Qianru, Deng Xuejian, Chen Huafeng, Liang Jiamin, An Min, Yang Li. Gene-modified stem cells therapy for osteoporosis: a meta-analysis of preclinical studies[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(31): 5053-5061.
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2.3 Meta分析结果 2.3.1 各组骨密度和BV/TV的差异 有19个研究报告了基因修饰干细胞相比于单纯干细胞对骨质疏松动物的骨密度的影响[5-11,13-23,26],各研究结果之间异质性较高(I2=85%,P < 0.01),选择随机效应模型,结果显示基因修饰干细胞组的骨密度明显高于单纯干细胞组(SMD=2.23,95%CI:1.34-3.11),见图4A。12个研究报告了基因修饰干细胞相比于单纯干细胞对骨质疏松动物的BV/TV的影响[8,9,12,14-16,18,20,23-26],各项研究结果之间有较高异质性(I2=76%,P < 0.01),选择随机效应模型,结果显示实验组的BV/TV高于对照组(SMD=1.95,95%CI:1.07-2.83),见图4B。"
2.3.2 各组Tb.N、Tb.Th和Tb.Sp的差异 有11个研究报告了基因修饰干细胞相比于单纯干细胞对骨质疏松动物的Tb.N的影响[8-9,12,14-16,18,20,23,25-26],各项研究之间存在较高异质性(I2=76%,P < 0.01),选择随机效应模型,结果显示实验组的Tb.N高于对照组(SMD=2.33,95%CI:1.34-3.32),见图5A。有10个研究报告了基因修饰干细胞相比于单纯干细胞对骨质疏松动物的Tb.Th的影响[9,12,14-16,18,20,23,25,26],各项研究之间存在较高异质性(I2=70%,P < 0.01),选择随机效应模型,结果显示实验组的Tb.Th高于对照组(SMD=1.47,95%CI:0.70-2.24),见图5B。9个研究报告了基因修饰干细胞相比于单纯干细胞对骨质疏松动物的Tb.Sp的影响[9,12,14,16,18,20,23,25-26],各项研究之间存在较高异质性(I2=84%,P < 0.01),选择随机效应模型,结果显示实验组的Tb.Sp低于对照组(SMD=-2.77,95%CI:-4.17至-1.36),见图5C。"
2.3.3 各组血钙、磷、骨碱性磷酸酶水平差异 有3个研究报告了基因修饰干细胞相比于单纯干细胞对骨质疏松动物的血钙的影响[11,22-23],各项研究无异质性(I2=0%,P=0.82),选择固定效应模型,结果显示实验组的血钙水平低于对照组(MD=-0.04,95%CI:-0.06至-0.03),见图6A。有3个研究报告了基因修饰干细胞相比于单纯干细胞对骨质疏松动物的血磷的影响[11,22-23],各项研究之间中度异质性(I2=60%),但差异无显著性意义(P=0.08),选择固定效应模型,结果显示实验组的血磷水平高于对照组(MD=0.10,95%CI:0.08-0.12),见图6B。3个研究报告了基因修饰干细胞相比于单纯干细胞对骨质疏松动物的血骨碱性磷酸酶的影响[11,22,24],各项研究无异质性(I2=0%,P=0.96),选择固定效应模型,结果显示实验组的血骨碱性磷酸酶水平低于对照组(MD=-4.46,95%CI:-5.12至-3.80),见图6C。"
2.3.4 骨密度、BV/TV、Tb.N、Tb.Th和Tb.Sp的亚组分析结果 根据干细胞、受试动物、干预时间、移植途径、修饰基因和测量部位的不同对骨组织形态计量学指标骨密度、BV/TV、Tb.N、Tb.Th和Tb.Sp结局指标进行亚组分析,见表3。结果显示:①干细胞分为骨髓间充质干细胞、脂肪源性干细胞和牙髓源性干细胞组,脂肪源性干细胞亚组中实验组与对照组的Tb.Th没有显著差异(P=0.09);②受试动物分为大鼠、小鼠和白兔组,小鼠亚组中实验组的Tb.N高于对照组(P=0.21);③干预时间分为≤4周、> 4周≤8周和> 8周组,在> 8周亚组中实验组的Tb.Th高于对照组(P=0.25),Tb.Sp明显小于对照组(P=0.61),在> 4周≤8周亚组中实验组和对照组的Tb.Th无显著差异(P=0.12);④移植途径分为腹膜腔内注射、尾静脉注射和局部注射填充组,腹膜腔内注射亚组中实验组的骨密度高于对照组(P=0.39),Tb.Th高于对照组(P=0.34);⑤修饰基因分为骨形态发生蛋白2、骨保护素、Rank-Fc、CXCR4和其他,骨形态发生蛋白2亚组中实验组的BV/TV高于对照组(P=0.05),两组的Tb.Th无显著差异(P=0.08);CXCR4亚组和Rank-Fc亚组中实验组和对照组之间无异质性(I2=0%,P > 0.05),但两组的骨密度无显著差异,95%CI分别为(-0.13-1.67)和(-0.44-1.02);⑥测量部位分为长骨和不规则骨组,其中不规则骨亚组中实验组和对照组具有低度异质性(I2=0.2%,P=0.20),但两组骨密度无明显差异;⑦其余亚组中实验组和对照组之间异质性明显(P < 0.05),差异与总体趋势一致。"
2.3.5 敏感性分析和发表偏倚分析结果 敏感性分析转换固定效应模型和随机效应模型对汇总效应量没有影响,逐一删除某个研究不会对合并效应量结果产生影响。除BV/TV分析的漏斗图基本对称之外,其余均存在一定的发表偏倚。血钙分析中纳入3个研究,Egger检测结果显示:t=-0.96,P=0.512 2,不存在发表偏倚;血磷分析中纳入3个研究,Egger检测结果显示:t=3.03,P=0.202 8,不存在发表偏倚;血骨碱性磷酸酶水平分析中纳入3个研究,Egger检测结果显示:t=-1.10,P=0.385 5,不存在发表偏倚。骨密度、BV/TV、Tb.N、Tb.Th、Tb.Sp的敏感性分析和发表偏倚漏斗图见图7。"
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