Naseri Mohammad Hassan, Madani Hoda, Ahmadi Tafti Seyed Hossein, Moshkani Farahani Maryam, Kazemi Saleh Davood, Hosseinnejad Hossein, Hosseini Saeid, Hekmat Sepideh, Hossein Ahmadi Zargham, Dehghani Majid, Saadat Alireza, Mardpour Soura, Hosseini Seyedeh Esmat, Esmaeilzadeh Maryam, Sadeghian Hakimeh, Bahoush Gholamreza, Bassi Ali, Amin Ahmad, Fazeli Roghayeh, Sharafi Yaser, Arab Leila, Movahhed Mansour, Davaran Saeid, Ramezanzadeh Narges, Kouhkan Azam, Hezavehei Ali, Namiri Mehrnaz, Kashfi Fahimeh, Akhlaghi Ali, Sotoodehnejadnematalahi Fattah, Vosough Dizaji Ahmad, Gourabi Hamid, Syedi Naeema, Shahverdi Abdol Hosein, Baharvand Hossein, Aghdami Nasser
Department of Surgery, Baqiyatallah Hospital, Tehran, Iran.
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Cell J. 2018 Jul;20(2):267-277. doi: 10.22074/cellj.2018.5197. Epub 2018 Mar 18.
The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft.
This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group×time interaction terms.
There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9% [95% confidence intervals (CI): 2.14% to 15.78%, P=0.01] and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points.
Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751).
骨髓来源的单个核细胞（MNCs）和CD133+干细胞在心脏中的再生潜力在其促血管生成作用方面存在差异。这项II/III期多中心双盲试验旨在比较这两种细胞类型与安慰剂心肌内自体移植对近期心肌梗死（RMI）患者冠状动脉旁路移植术后的功能影响。
这是一项II/III期随机双盲安慰剂对照试验COMPARE CPM-RMI（CD133、安慰剂、MNCs - 近期心肌梗死），按照《赫尔辛基宣言》进行，评估了CD133和MNCs与安慰剂相比在RMI患者中的安全性和有效性。我们从5家医院随机分配了77名符合条件的RMI患者，分别接受CD133+细胞、MNC或安慰剂。患者在心肌内移植后6个月和18个月接受门控单光子发射计算机断层扫描评估。我们使用方差混合分析模型对正态分布的疗效结果进行了测试，该模型使用了基线的整个数据集以及组间比较以及受试者内（时间）和组×时间交互项。
未报告相关严重不良事件。两种细胞类型的心肌内移植均使左心室射血分数提高了9%[95%置信区间（CI）：2.14%至15.78%，P = 0.01]，并改善了收缩期室壁增厚减少的情况，减少了-3.7（95%CI：-7.07至-0.42，P = 0.03）。与安慰剂相比，CD133组的无存活节段显著减少了75%（P = 0.），与MNC组相比减少了60%（P = 0.01）。我们在6个月和18个月的时间点均观察到了这种改善。
对于RMI患者，心肌内注射CD133+细胞或MNCs似乎是安全有效的，且CD133+细胞具有优势。尽管样本量不足以对临床结果做出明确陈述，但这些结果为更大规模研究提供了基础，以确认这些细胞类型疗效的确切证据（注册号：NCT01167751）。
