来自香港大学Tse报告了第一项随机、对照的直接将干细胞注入心肌治疗慢性缺血性心肌病的临床试验。该研究包括经心肌/经冠脉不同途径注入干细胞,同时尝试了干细胞的替代来源,包括脐带血或经血等。
PROTECT-CAD试验中“假操作”(对照组)是有决定性意义的,无安全性问题。Tse解释了该试验与既往大多数有关急性心肌梗死研究的不同之处。该研究入选“无选择”的慢性缺血性心脏病患者,即经过最佳的药物治疗后仍存在3~4级心绞痛症状的患者。
28例患者随机按2∶1比例接受1~2个剂量的干细胞或“安慰剂-盐水”注入治疗。所有患者均从髂脊抽取干细胞,采用3D NOGA地图系统(Biosense Webster,Diamond Bar,CA)经导管直接注入目标缺血心肌;对照组接受心肌盐水注入,而不注入干细胞。这种“独特”的操作全部完成大概需要几个小时,患者可于注射完成后第二天回家。主要终点是6个月时的运动试验时间;次要终点包括磁共振成像(MRI)测定的左室射血分数(LVEF),单光子发射计算机断层扫描 (SPECT)测定心肌灌注以及采用各种方法进行的安全性监测。
试验中19例患者接受干细胞治疗,9例接受盐水注入。细胞治疗组运动时间显著增加20.9%,“对照组”减少了18%(P=0.026)。干细胞治疗组的 LVEF显著增加(7.6%对4.6%,P<0.01),同时细胞治疗组负荷诱发的心肌灌注减少31%,而安慰剂组却增加了26%(P= 0.04)。
从上述结果可以看出,干细胞注入是安全的——未发现肿瘤发生,心律失常、心肌钙化以及猝死等。Tse还指出,直接经心内膜注入可使11%的干细胞到达心肌部位,而经冠脉注入法仅有2%可到达心肌。
http://www.cmt.com.cn/article/060427/a0604273501.htmCAD therapy: Bone marrow cell injection
Dr. Hung-Fat Tse, University of Hong Kong, Hong Kong, China
The direct injection of bone marrow cells into heart tissue appears to improve several measures of heart function for patients with severe CAD, Dr. Tse began.
The potential of stem cells to heal damaged heart tissue is attractive because, “despite advances in medical therapy and coronary revascularization techniques, a significant percentage of patients with CAD have failed or incomplete revascularization and suffered from refractory angina,” Dr. Tse said.
Previous experimental and non-randomized pilot studies demonstrated possible improvements in myocardial perfusion with this technique.
Dr. Tse and colleagues therefore undertook the Prospective Randomized Trial of Direct Myocardial Implantation of Bone Marrow Cells for Therapeutic Angiogenesis in Coronary Artery Disease (PROTECT-CAD).
For this, they recruited 28 patients with severe CAD that could not be treated with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, randomizing them to bone marrow implantation or a sham procedure involving the injection of saline. The bone marrow cell injection group was further randomized into two dose groups: 1x107 and 2x107 cells/mL.
Bone marrow cells were collected from the iliac crest bone of each patient, separated using a density gradient centrifuge, and injected back into the patient’s damaged myocardium using electromechanical maps to guide injection. A catheter with a needle on the tip was used to inject the cells.
Patients in the control group were more likely to have had a PCI (89% versus 47%) and diabetes (67% versus 42%). Other baseline characteristics were similar.
In all, 27 patients received a total of 422 injections to 41 ischemic regions, with a mean of 14.6 injections. One patient in the control group failed to receive treatment injections because vascular access to the left ventricular failed.
Exercise time, which was the primary endpoint, increased by 20.9% in the bone marrow cell group over 6 months, compared with a decrease of 18% in the placebo group. This represented significant improvement for patients in the bone marrow cell group, both in comparison with placebo group (p=0.026) and baseline values (p=0.05).
There was no significant dose response seen in the bone marrow cell group.
The left ventricular ejection fraction improved by 7.6% in the bone marrow cell group (a significant rise over baseline), versus 4.6% for placebo-treated patients. Stress induced myocardial ischemia was also reduced 30% compared to placebo.
No acute or long-term adverse effects were observed for pro-arrhythmia, tumor formation, or intramyocardial calcification. There were no cases of pericardial effusion, significant elevation in cardiac enzyme or acute ventricular arrhythmias.
