富血小板血浆联合脂肪干细胞移植加速伤口愈合的临床前研究:系统评价和Meta分析

Preclinical study of platelet-rich plasma combined with adipose stem cell transplantation in accelerating wound healing:a systematic evaluation and meta-analysis

目的:研究表明,富血小板血浆和脂肪来源干细胞的组合可加速皮肤损伤的愈合,但仍缺乏二者联合治疗的系统证据。该文评价两种干预措施在临床啮齿动物皮肤创伤模型中的联合疗效。方法:检索PubMed、Embase和Cochrane及CNKI数据库,选择各数据库建库至2023年7月发表的富血小板血浆与脂肪干细胞移植联合使用以及单独使用于实验动物皮肤伤口的研究,以伤口愈合及伤口中转化生长因子β、CD31、Ⅰ型胶原蛋白和血管内皮生长因子为观察指标,使用RevMan 5.3和Stata 15.0软件对数据进行Meta分析。结果:共纳入12项研究,其中8项研究使用大鼠作为实验对象,4项研究使用小鼠作为实验对象,实验组采用富血小板血浆联合脂肪干细胞移植治疗,对照组采用单独的富血小板血浆治疗。Meta分析结果显示,实验组治疗后第3,7,10天的伤口愈合率均大于对照组[SMD=2.65,95%CI(1.29,4.01),Z=3.81,P=0.0001;SMD=3.38,95%CI(2.47,4.30),Z=7.24,P<0.00001;SMD=2.62,95%CI(1.50,3.73),Z=4.61,P<0.00001],实验组伤口愈合时间短于对照组[SMD=-2.12,95%CI(-3.5,-0.74),P=0.003],实验组伤口中的转化生长因子β表达、CD31阳性率、Ⅰ型胶原蛋白及血管内皮生长因子表达均高于对照组[SMD=5.65,95%CI(1.22,10.08),Z=2.50,P=0.01;SMD=2.49,95%CI(1.96,3.02),Z=9.28,P<0.00001;SMD=3.44,95%CI(0.72,6.17),Z=2.48,P=0.01;SMD=2.38,95%CI(0.97,3.79),Z=3.30,P=0.0010]。结论:研究结果表明,富血小板血浆与脂肪干细胞联合治疗可提高伤口愈合率、缩短伤口愈合时间,同时增加转化生长因子β、CD31、Ⅰ型胶原蛋白和血管内皮生长因子的表达,加速伤口愈合。由于模型的局限性,需要进行更多的动物实验和临床试验进行进一步证实。

OBJECTIVE:Researches show that a combination of platelet-rich plasma and adipose-derived stem cells can accelerate the healing of skin lesions.However,systematic evidence for the combination of the two is still lacking.The purpose of this study was to assess the efficacy of a combination of two interventions in a clinical rodent skin wound model.METHODS:We searched PubMed,Embase,Cochrane,and CNKI and selected the studies of platelet-rich plasma,adipose-derived stem cell transplantation,or their combination on skin wounds in experimental animals published until July 2023.Wound healing and wound transformation growth factorβ,CD31,type I collagen,and vascular endothelial growth factor were used as indicators.RevMan 5.3 and Stata 15.0 were used to analyze the data.RESULTS:A total of 12 studies were included,of which 8 studies used rats as experimental subjects and 4 studies used mice as experimental subjects.The experimental group was treated with platelet-rich plasma combined with adipose-stem cell transplantation,and the control group was treated with platelet-rich plasma alone.The results of meta-analysis showed that the wound healing rate of the experimental group at 3,7,and 10 days after treatment was greater than that of the control group[SMD=2.65,95%CI(1.29,4.01),Z=3.81,P=0.0001;SMD=3.38,95%CI(2.47,4.30),Z=7.24,P<0.00001;SMD=2.62,95%CI(1.50,3.73),Z=4.61,P<0.00001].The wound healing time of the experimental group was shorter than that of the control group[SMD=-2.12,95%CI(-3.5,-0.74),P=0.003].The expression of transforming growth factorβ,positive rate of CD31,expression of type I collagen,and vascular endothelial growth factor in wound of experimental group were higher than those of control group[SMD=5.65,95%CI(1.22,10.08),Z=2.50,P=0.01;SMD=2.49,95%CI(1.96,3.02),Z=9.28,P<0.00001;SMD=3.44,95%CI(0.72,6.17),Z=2.48,P=0.01;SMD=2.38,95%CI(0.97,3.79),Z=3.30,P=0.0010].CONCLUSION:Our results show that platelet-rich plasma+adipose-derived stem cells combined treatment can improve the wound healing rate,shorten the wound healing time,and at the same time increase the expression of transforming growth factorβ,CD31,type I collagen,and vascular endothelial growth factor to accelerate healing.Due to the limitations of the model,more animal testing and clinical trials are needed.