Rationale: Umbilical cord–derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow–derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients.

Objective: Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction.

Methods and Results: Patients with heart failure and reduced ejection fraction under optimal medical treatment were randomized to intravenous infusion of allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile; 1×10⁶ cells/kg) or placebo (n=15 per group). UC-MSCs in vitro, compared with bone marrow–derived mesenchymal stem cells, displayed a 55-fold increase in the expression of hepatocyte growth factor, known to be involved in myogenesis, cell migration, and immunoregulation. UC-MSC–treated patients presented no adverse events related to the cell infusion, and none of the patients tested at 0, 15, and 90 days presented alloantibodies to the UC-MSCs (n=7). Only the UC-MSC–treated group exhibited significant improvements in left ventricular ejection fraction at 3, 6, and 12 months of follow-up assessed both through transthoracic echocardiography (P=0.0167 versus baseline) and cardiac MRI (P=0.025 versus baseline). Echocardiographic left ventricular ejection fraction change from baseline to month 12 differed significantly between groups (+7.07±6.22% versus +1.85±5.60%; P=0.028). In addition, at all follow-up time points, UC-MSC–treated patients displayed improvements of New York Heart Association functional class (P=0.0167 versus baseline) and Minnesota Living with Heart Failure Questionnaire (P<0.05 versus baseline). At study completion, groups did not differ in mortality, heart failure admissions, arrhythmias, or incident malignancy.

Conclusions: Intravenous infusion of UC-MSC was safe in this group of patients with stable heart failure and reduced ejection fraction under optimal medical treatment. Improvements in left ventricular function, functional status, and quality of life were observed in patients treated with UC-MSCs.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT01739777. Unique identifier: NCT01739777

原理：脐带间充质干细胞（UC-MSC）易于在体外获得和扩增，具有独特的特性，并改善了心血管疾病实验模型中的心肌重塑和功能。尽管先前已经评估了源自骨髓的间充质干细胞在患有心力衰竭和射血分数降低的个体中的治疗潜力，但尚无临床试验评估这些患者的静脉输注UC-MSC。

目的：评估静脉注射UC-MSC在慢性稳定型心力衰竭和射血分数降低的患者中的安全性和有效性。

方法和结果：在最佳治疗下患有心力衰竭和射血分数降低的患者被随机分配为同种异体UC-MSC的静脉输注（Cellistem，智利Cells for Cells SA； 1×10 ^6）细胞/千克）或安慰剂（每组n = 15）。与骨髓来源的间充质干细胞相比，体外UC-MSCs的肝细胞生长因子表达增加了55倍，已知其参与肌发生，细胞迁移和免疫调节。UC-MSC治疗的患者未出现与细胞输注相关的不良事件，在0、15和90天接受测试的患者均未出现针对UC-MSC的同种抗体（n = 7）。仅经UC-MSC治疗的组在经胸超声心动图（相对于基线，P = 0.0167）和心脏MRI（P = 0.0167）评估的随访3、6和12个月时，左心室射血分数显着改善。= 0.025（相对于基线）。各组之间从基线到第12个月的超声心动图左室射血分数变化差异显着（+ 7.07±6.22％对+ 1.85±5.60％；P = 0.028）。此外，在所有随访时间点，接受UC-MSC治疗的患者的纽约心脏协会功能等级（相对于基线，P = 0.0167）和明尼苏达州心衰患者问卷调查（相对于基线，P <0.05）均有改善。在研究完成时，各组的死亡率，心力衰竭入院率，心律不齐或恶性肿瘤的发生率无差异。

结论： UC-MSC静脉输注在经过最佳药物治疗的稳定心力衰竭和射血分数降低的患者中是安全的。UC-MSCs治疗的患者左心室功能，功能状态和生活质量得到改善。

临床试验注册： URL： https : //www.clinicaltrials.gov/ct2/show/NCT01739777。唯一标识符：NCT01739777