Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]).
Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]).
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DOI：
10.1161/circresaha.117.310712
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发表时间：
2017-10-27
影响因子：
20.1
通讯作者：
Khoury M
中科院分区：
文献类型：
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作者：
Bartolucci J;Verdugo FJ;González PL;Larrea RE;Abarzua E;Goset C;Rojo P;Palma I;Lamich R;Pedreros PA;Valdivia G;Lopez VM;Nazzal C;Alcayaga-Miranda F;Cuenca J;Brobeck MJ;Patel AN;Figueroa FE;Khoury M
文本中提供了补充数字内容。脐带间充质干细胞 (UC-MSC) 易于在体外获取和扩增，具有独特的特性，可改善心血管疾病实验模型中的心肌重塑和功能。尽管先前已评估了骨髓间充质干细胞对心力衰竭和射血分数降低患者的治疗潜力，但尚无临床试验评估这些患者静脉输注 UC-MSC 的情况。评估静脉输注 UC-MSC 对射血分数降低的慢性稳定性心力衰竭患者的安全性和有效性。接受最佳药物治疗的心力衰竭和射血分数降低的患者被随机分配接受同种异体 UC-MSC 静脉输注（Cellistem，Cells for Cells S.A.，圣地亚哥，智利；1×106 个细胞/kg）或安慰剂（每组 n = 15）。与骨髓间充质干细胞相比，体外 UC-MSC 的肝细胞生长因子表达增加了 55 倍，已知该因子参与肌生成、细胞迁移和免疫调节。 UC-MSC 治疗的患者没有出现与细胞输注相关的不良事件，并且在第 0、15 和 90 天测试的患者中没有一人出现针对 UC-MSC 的同种抗体 (n=7)。通过经胸超声心动图（与基线相比，P=0.0167）和心脏 MRI（与基线相比，P=0.025）评估，只有 UC-MSC 治疗组在 3、6 和 12 个月的随访中表现出左心室射血分数显着改善。超声心动图左心室射血分数从基线到第 12 个月的变化在各组之间存在显着差异（+7.07±6.22% 与 +1.85±5.60%；P=0.028）。此外，在所有随访时间点，UC-MSC 治疗的患者均表现出纽约心脏协会功能分级（与基线相比，P=0.0167）和明尼苏达心力衰竭生活问卷（与基线相比，P<0.05）的改善。研究完成时，各组在死亡率、心力衰竭入院率、心律失常或恶性肿瘤方面没有差异。对于本组在最佳治疗下出现稳定心力衰竭且射血分数降低的患者，静脉输注 UC-MSC 是安全的。在接受 UC-MSC 治疗的患者中观察到左心室功能、功能状态和生活质量的改善。网址：https://www.clinicaltrials.gov/ct2/show/NCT01739777。唯一标识符：NCT01739777
Supplemental Digital Content is available in the text. 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. Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction. 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. 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. URL: https://www.clinicaltrials.gov/ct2/show/NCT01739777. Unique identifier: NCT01739777