Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.
Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial.
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DOI：
10.1001/jama.2012.25321
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发表时间：
2012-12-12
期刊：
影响因子：
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通讯作者：
Lardo A
中科院分区：
文献类型：
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作者：
Hare JM;Fishman JE;Gerstenblith G;DiFede Velazquez DL;Zambrano JP;Suncion VY;Tracy M;Ghersin E;Johnston PV;Brinker JA;Breton E;Davis-Sproul J;Schulman IH;Byrnes J;Mendizabal AM;Lowery MH;Rouy D;Altman P;Wong Po Foo C;Ruiz P;Amador A;Da Silva J;McNiece IK;Heldman AW;George R;Lardo A
间充质干细胞（MSC）作为缺血性心肌病（ICM）的治疗方法正在接受评估。自体和同种异体 MSC 疗法都是可能的；然而，它们的安全性和有效性尚未进行比较。测试异体 MSC 是否与自体 MSC 一样安全有效地治疗 ICM 引起的左心室 (LV) 功能障碍。 2010年4月2日至2011年9月14日期间，美国一家三级转诊医院对30名因ICM导致左室功能障碍的患者进行了同种异体和自体间充质干细胞的1/2期随机比较（POSEIDON研究），并进行了13个月的随访。通过经心内膜干细胞注射将 2000 万、1 亿或 2 亿个细胞（每个剂量水平每种细胞类型 5 名患者）输送到 10 个左心室部位。导管插入后 30 天预定义的治疗中出现的严重不良事件 (SAE) 的发生率。功效评估包括 6 分钟步行测试、运动峰值、明尼苏达心力衰竭问卷 (MLHFQ)、纽约心脏协会分级、左心室容量、射血分数 (EF)、早期增强缺陷 (EED；梗塞面积) 和球形指数。 30 天内，每组有 1 名患者（治疗中出现的 SAE 发生率为 6.7%）因心力衰竭住院，低于预先设定的 25% 的停止事件发生率。同种异体组中 SAE 的 1 年发生率为 33.3% (n=5)，自体组中为 53.3% (n=8) (P=.46)。 1 年时，同种异体受者中没有观察到室性心律失常 SAE，而自体受者组中有 4 名患者 (26.7%) 出现 (P=.10)。相对于基线，自体而非同种异体 MSC 治疗与 6 分钟步行测试和 MLHFQ 评分的改善相关，但两者均未改善最大运动量。同种异体和自体 MSC 使平均 EED 降低了 -33.21%（95% CI，-43.61% 至 -22.81%；P<.001）和球形指数，但没有增加 EF。同种异体 MSC 降低了左心室舒张末期容积。低剂量浓度的 MSC（2000 万个细胞）可最大程度地减少 LV 体积并增加 EF。同种异体 MSC 不会刺激显着的供体特异性同种免疫反应。在这项针对 ICM 患者的早期研究中，在没有安慰剂对照的情况下经心内膜注射同种异体和自体 MSC 均与治疗引起的 SAE（包括免疫反应）的低发生率相关。总的来说，间充质干细胞注射对患者的功能能力、生活质量和心室重塑产生了有利的影响。 ClinicalTrials.gov 标识符：NCT01087996
Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM. A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak , Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index. Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n=5) in the allogeneic group and 53.3% (n=8) in the autologous group (P=.46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P=.10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P<.001) and sphericity index but did not increase EF. Allogeneic MSCs reduced LV end-diastolic volumes. Low-dose concentration MSCs (20 million cells) produced greatest reductions in LV volumes and increased EF. Allogeneic MSCs did not stimulate significant donor-specific alloimmune reactions. In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. clinicaltrials.gov Identifier: NCT01087996