PDF(Pubmed)
Abstract：
BACKGROUND: Mesenchymal stem cells (MSCs) have emerged as living biodrugs for myocardial repair and regeneration. Recent randomized controlled trials (RCTs) have reported that MSC-based therapy is safe and effective in heart failure patients; however, its dose-response relationship has yet to be established. We aimed to determine the optimal MSC dose for treating HF patients with reduced ejection fraction (EF) (HFrEF).
METHODS: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane Handbook guidelines were followed. Four databases and registries, i.e., PubMed, EBSCO, clinicaltrials.gov, ICTRP, and other websites, were searched for RCTs. Eleven RCTs with 1098 participants (treatment group, n = 606; control group, n = 492) were selected based on our inclusion/exclusion criteria. Two independent assessors extracted the data and performed quality assessments. The data from all eligible studies were plotted for death, major adverse cardiac events (MACE), left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and 6-minute walk distance (6-MWD) as safety, efficacy, and performance parameters. For dose-escalation assessment, studies were categorized as low-dose (< 100 million cells) or high-dose (≥ 100 million cells).
RESULTS: MSC-based treatment is safe across low and high doses, with nonsignificant effects. However, low-dose treatment had a more significant protective effect than high-dose treatment. Subgroup analysis revealed the superiority of low-dose treatment in improving LVEF by 3.01% (95% CI; 0.65-5.38%) compared with high-dose treatment (-0.48%; 95% CI; -2.14-1.18). MSC treatment significantly improved the 6-MWD by 26.74 m (95% CI; 3.74-49.74 m) in the low-dose treatment group and by 36.73 m (95% CI; 6.74-66.72 m) in the high-dose treatment group. The exclusion of studies using ADRCs resulted in better safety and a significant improvement in LVEF from low- and high-dose MSC treatment.
CONCLUSIONS: Low-dose MSC treatment was safe and superior to high-dose treatment in restoring efficacy and functional outcomes in heart failure patients, and further analysis in a larger patient group is warranted.
METHODS: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane Handbook guidelines were followed. Four databases and registries, i.e., PubMed, EBSCO, clinicaltrials.gov, ICTRP, and other websites, were searched for RCTs. Eleven RCTs with 1098 participants (treatment group, n = 606; control group, n = 492) were selected based on our inclusion/exclusion criteria. Two independent assessors extracted the data and performed quality assessments. The data from all eligible studies were plotted for death, major adverse cardiac events (MACE), left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and 6-minute walk distance (6-MWD) as safety, efficacy, and performance parameters. For dose-escalation assessment, studies were categorized as low-dose (< 100 million cells) or high-dose (≥ 100 million cells).
RESULTS: MSC-based treatment is safe across low and high doses, with nonsignificant effects. However, low-dose treatment had a more significant protective effect than high-dose treatment. Subgroup analysis revealed the superiority of low-dose treatment in improving LVEF by 3.01% (95% CI; 0.65-5.38%) compared with high-dose treatment (-0.48%; 95% CI; -2.14-1.18). MSC treatment significantly improved the 6-MWD by 26.74 m (95% CI; 3.74-49.74 m) in the low-dose treatment group and by 36.73 m (95% CI; 6.74-66.72 m) in the high-dose treatment group. The exclusion of studies using ADRCs resulted in better safety and a significant improvement in LVEF from low- and high-dose MSC treatment.
CONCLUSIONS: Low-dose MSC treatment was safe and superior to high-dose treatment in restoring efficacy and functional outcomes in heart failure patients, and further analysis in a larger patient group is warranted.
摘要：
背景：间充质干细胞（MSCs）已成为心肌修复和再生的活生物药物。最近的随机对照试验（RCTs）报道，基于MSC的治疗对心力衰竭患者是安全有效的；然而，其剂量-反应关系尚未确定。我们旨在确定治疗射血分数（EF）（HFrEF）降低的HF患者的最佳MSC剂量。
方法：遵循系统评价和荟萃分析（PRISMA）和Cochrane手册指南的首选报告项目。四个数据库和登记册，即，PubMed,EBSCO,clinicaltrials.gov,ICTRP,和其他网站，搜索RCT。11项随机对照试验，1098名参与者（治疗组，n=606；对照组，n=492)是根据我们的纳入/排除标准选择的。两名独立评估员提取数据并进行质量评估。所有符合条件的研究的数据都是针对死亡绘制的，主要不良心脏事件（MACE），左心室射血分数(LVEF),左心室收缩末期容积(LVESV),和6分钟步行距离（6-MWD）作为安全，功效,和性能参数。对于剂量递增评估，研究分为低剂量（<1亿个细胞）或高剂量（≥1亿个细胞）。
结果：基于MSC的治疗在低剂量和高剂量下都是安全的，效果不显著。然而,低剂量治疗比高剂量治疗具有更显著的保护作用.亚组分析显示，与高剂量治疗（-0.48％;95％CI;-2.14-1.18）相比，低剂量治疗在改善LVEF方面的优势为3.01％（95％CI;0.65-5.38％）。MSC治疗在低剂量治疗组中显著改善了6-MWD26.74m(95%CI;3.74-49.74m),在高剂量治疗组中显著改善了36.73m(95%CI;6.74-66.72m)。排除使用ADRCs的研究导致更好的安全性和低和高剂量MSC治疗的LVEF的显著改善。
结论：低剂量MSC治疗是安全的，在恢复心力衰竭患者的疗效和功能结局方面优于高剂量治疗。需要在更大的患者组中进行进一步分析.
方法：遵循系统评价和荟萃分析（PRISMA）和Cochrane手册指南的首选报告项目。四个数据库和登记册，即，PubMed,EBSCO,clinicaltrials.gov,ICTRP,和其他网站，搜索RCT。11项随机对照试验，1098名参与者（治疗组，n=606；对照组，n=492)是根据我们的纳入/排除标准选择的。两名独立评估员提取数据并进行质量评估。所有符合条件的研究的数据都是针对死亡绘制的，主要不良心脏事件（MACE），左心室射血分数(LVEF),左心室收缩末期容积(LVESV),和6分钟步行距离（6-MWD）作为安全，功效,和性能参数。对于剂量递增评估，研究分为低剂量（<1亿个细胞）或高剂量（≥1亿个细胞）。
结果：基于MSC的治疗在低剂量和高剂量下都是安全的，效果不显著。然而,低剂量治疗比高剂量治疗具有更显著的保护作用.亚组分析显示，与高剂量治疗（-0.48％;95％CI;-2.14-1.18）相比，低剂量治疗在改善LVEF方面的优势为3.01％（95％CI;0.65-5.38％）。MSC治疗在低剂量治疗组中显著改善了6-MWD26.74m(95%CI;3.74-49.74m),在高剂量治疗组中显著改善了36.73m(95%CI;6.74-66.72m)。排除使用ADRCs的研究导致更好的安全性和低和高剂量MSC治疗的LVEF的显著改善。
结论：低剂量MSC治疗是安全的，在恢复心力衰竭患者的疗效和功能结局方面优于高剂量治疗。需要在更大的患者组中进行进一步分析.
