这项荟萃分析和系统评价汇编了2004年至2024年的比较数据,研究了源自各种组织的间充质干细胞/基质细胞(MSC)用于治疗缺血性心肌病(ICM)和相关心力衰竭的安全性和有效性。此外,这篇综述强调了这些干预措施的局限性,并为未来的治疗方法提供了有价值的见解.使用目标关键词从PubMed®数据库检索相关文章。我们的纳入标准包括18岁以上患者的临床试验,病例报告和试点研究。动物实验,体外研究,相关和纵向研究,研究设计和方案被排除.49篇原始文章导致45项试验的随访报告。骨髓间充质干细胞,脐带和脂肪组织的耐受性中等。在接受MSC的1408名参与者中,33项试验(67.3%)报告了死亡或严重不良事件的发生。这些事件在MSC施用后导致80例死亡(占报告病例的52%)。重要的是,这些死亡中有41.3%(n=33)被认为与干预本身无关,而这些死亡中有40%没有报告原因。作为主要结果,左心室射血分数(LVEF)从基线平均增加5.75%(95%CI:3.38%-8.11%,p<0.0001,I2=90,9%)仅在治疗组中的随机对照试验(n=24)和3.19%(95%CI:1.63%至4.75%,干预后对照组p<0.0001,I2=74,17%)。当使用标准化平均差(SDM)比较上述结果时,也发现了有利于治疗组的显著性(SDM=0.41;95%CI:0.19-0.64,p<0.001,I2=71%)。尽管对照组也有改善,33.3%(n=15)的研究显示对照组和治疗组之间没有显著差异。6分钟步行测试(6MWT)和纽约心脏协会(NYHA)课程成绩,用于评估运动耐量和生活质量(QoL),分别,进一步支持治疗组的改善.6MWT的这些改进为62.5%(n=10),NYHA等级分数为54.5%(n=12)。根据风险偏差分析,4个试验质量良好(11.8%),15人质量一般(44.1%),质量差15例(44.1%)。这些研究的主要局限性包括样本量小,诊断挑战/缺乏,不确定的细胞剂量和患者选择的潜在偏差。尽管围绕ICM的细胞管理一直存在争论,有临床和实验室结果改善的支持迹象,以及改善MSC治疗组的QoL。然而,重要的是要认识到每一项研究的局限性,强调对更大的需求,对照试验来验证这些发现。
This meta-analysis and systematic
review compiles comparative data from 2004 to 2024, investigating the safety and efficacy of mesenchymal stem/stromal cells (MSCs) derived from various tissues for the treatment of ischemic cardiomyopathy (ICM) and associated heart failure. In addition, this
review highlights the limitations of these interventions and provides valuable insights for future therapeutic approaches. Relevant articles were retrieved from the PubMed® database using targeted keywords. Our inclusion criteria included clinical trials with patients over 18 years of age, case reports and pilot studies. Animal experiments, in vitro studies, correlational and longitudinal studies, and study designs and protocols were excluded. Forty-nine original articles resulted in follow-up reports of 45 trials. MSCs from bone marrow, umbilical cord and adipose tissue were moderately well tolerated. Of the 1408 participants who received MSCs, 33 trials (67.3%) reported the occurrence of death or serious adverse events. These events resulted in 80 deaths (52% of reported cases) following MSC administration. Importantly, 41.3% of these deaths (n = 33) were not considered to be related to the intervention itself, while 40% of these deaths had no reported cause. As the primary outcome, the mean increase in left ventricular ejection fraction (LVEF) from baseline was 5.75% (95% CI: 3.38% -8.11%, p < 0.0001, I2 = 90,9%) in the randomized controlled trials only (n = 24) within the treatment groups and 3.19% (95% CI: 1.63% to 4.75%, p < 0.0001, I2 = 74,17%) in the control groups after the intervention. When the above results were compared using the standardized mean difference (SDM), a significance in favor of the treatment group was also found (SDM = 0.41; 95% CI: 0.19-0.64, p < 0.001, I2 = 71%). Although improvements were also seen in the control groups, 33.3% (n = 15) of the studies showed no significant difference between the control and treatment groups. The 6-minute walking test (6MWT) and New York Heart Association (NYHA) class scores, used for assessing exercise tolerance and quality of life (QoL), respectively, further supported the improvements in the treatment group. These improvements were noted as 62.5% (n = 10) for the 6MWT and 54.5% (n = 12) for the NYHA class scores. According to the risk of bias analysis, 4 trials were of good quality (11.8%), 15 were of fair quality (44.1%), and 15 were of poor quality (44.1%). Major limitations of these studies included small sample size, diagnostic challenges/lack, uncertain cell dosage and potential bias in patient selection. Despite the ongoing debate surrounding cell administration for ICM, there are supporting signs of improved clinical and laboratory outcomes, as well as improved QoL in the MSC-treated groups. However, it is important to recognize the limitations of each study, highlighting the need for larger, controlled trials to validate these findings.