静脉内同种异体间充质干细胞治疗非缺血性心肌病：一项 II-A 期随机试验的安全性和疗效结果。
Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy: Safety and Efficacy Results of a Phase II-A Randomized Trial.
机构信息
From the Division of Cardiology, Department of Medicine, Stony Brook University, NY (J.B., H.A.S.); MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (S.E.E., M.J.L.); Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC (S.J.G., R.J.K.); Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA (A.A.Q., R.T.C.); CardioCell LLC, San Diego, CA (S.S.); Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (A.S.A., J.E.W.); Stemedica Cell Technologies Inc, San Diego, CA (N.I.T.); Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA (Y.-A.K.); Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (K.B.M.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (M.G.).
出版信息
Circ Res. 2017 Jan 20;120(2):332-340. doi: 10.1161/CIRCRESAHA.116.309717. Epub 2016 Nov 16.
RATIONALE
Potential benefits of mesenchymal stem cell (MSC) therapy in heart failure may be related to paracrine properties and systemic effects, including anti-inflammatory activities. If this hypothesis is valid, intravenous administration of MSCs should improve outcomes in heart failure, an entity in which excessive chronic inflammation may play a pivotal role.
OBJECTIVE
To assess the safety and preliminary efficacy of intravenously administered ischemia-tolerant MSCs (itMSCs) in patients with nonischemic cardiomyopathy.
METHODS AND RESULTS
This was a single-blind, placebo-controlled, crossover, randomized phase II-a trial of nonischemic cardiomyopathy patients with left ventricular ejection fraction ≤40% and absent hyperenhancement on cardiac magnetic resonance imaging. Patients were randomized to intravenously administered itMSCs (1.5×10 cells/kg) or placebo; at 90 days, each group received the alternative treatment. Overall, 22 patients were randomized to itMSC (n=10) and placebo (n=12) at baseline. After crossover, data were available for 22 itMSC patients. No major differences in death, hospitalization, or serious adverse events were noted between the 2 treatments. Change from baseline in left ventricular ejection fraction and ventricular volumes was not significantly different between therapies. Compared with placebo, itMSC therapy increased 6-minute walk distance (+36.47 m, 95% confidence interval 5.98-66.97; P=0.02) and improved Kansas City Cardiomyopathy clinical summary (+5.22, 95% confidence interval 0.70-9.74; P=0.02) and functional status scores (+5.65, 95% confidence interval -0.11 to 11.41; P=0.06). The data demonstrated MSC-induced immunomodulatory effects, the magnitude of which correlated with improvement in left ventricular ejection fraction.
CONCLUSIONS
In this pilot study of patients with nonischemic cardiomyopathy, itMSC therapy was safe, caused immunomodulatory effects, and was associated with improvements in health status and functional capacity.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02467387.
背景
间充质干细胞（MSC）治疗心力衰竭的潜在益处可能与旁分泌特性和全身效应有关，包括抗炎活性。如果这一假设成立，静脉内给予 MSC 应该能改善心力衰竭患者的预后，在心力衰竭中，过度的慢性炎症可能起着关键作用。
目的
评估静脉内给予耐缺血 MSC（itMSC）治疗非缺血性心肌病患者的安全性和初步疗效。
方法和结果
这是一项单盲、安慰剂对照、交叉、随机的 IIa 期临床试验，纳入左心室射血分数≤40%且心脏磁共振成像上无高增强的非缺血性心肌病患者。患者被随机分为静脉内给予 itMSC（1.5×10细胞/kg）或安慰剂；90 天后，每组接受替代治疗。共有 22 例患者在基线时被随机分为 itMSC（n=10）和安慰剂（n=12）组。交叉后，有 22 例 itMSC 患者的数据可用。两种治疗方法之间在死亡、住院或严重不良事件方面没有显著差异。与治疗前相比，两种治疗方法的左心室射血分数和心室容积变化均无显著差异。与安慰剂相比，itMSC 治疗可增加 6 分钟步行距离（+36.47m，95%置信区间 5.98-66.97；P=0.02），并改善堪萨斯城心肌病临床总结评分（+5.22，95%置信区间 0.70-9.74；P=0.02）和功能状态评分（+5.65，95%置信区间 -0.11 至 11.41；P=0.06）。数据显示 MSC 诱导了免疫调节作用，其程度与左心室射血分数的改善相关。
结论
在这项非缺血性心肌病患者的初步研究中，itMSC 治疗是安全的，引起了免疫调节作用，并与健康状况和功能能力的改善相关。
Zotero 插件