经冠状动脉自体骨髓间充质干细胞移植治疗急性心肌梗死:3个月疗效随访

背景:急性心肌梗死预后的决定因素是心肌梗死的面积。减少梗死面积的方法有改善血运和替代治疗。骨髓间充质干细胞可以分化为心血管组织,而且获取容易体外培养扩增,成为心血管替代治疗的理想细胞。目的:评价经冠状动脉人骨髓间充质干细胞移植治疗心肌梗死的疗效。设计:患者自身前后对照观察。单位:南京医科大学附属南京第一医院心内科、核医学科、超声心动图室。对象:选择2003-03/2004-03南京医科大学附属南京第一医院心内科收治的急性心肌梗死进行骨髓间充质干细胞移植治疗患者20例。患者知情同意,术后完整随访>3个月。男15例,女5例,平均年龄(64±10)岁。方法:①20例患者,均行经皮冠状动脉介入治疗治疗梗死相关血管。术后3d内采集患者自体骨髓,提取干细胞体外诱导、分化、增殖。2周内经冠状动脉植入梗死相关血管,平均植入干细胞数量为(21.7±30.14)×107。②干细胞植入前及术后3个月行门控双核素心肌灌注/代谢显像(18F-脱氧葡萄糖,18F-FDG)检查,预测存活及坏死心肌,并获取梗死面积。同时行超声心动图检查评价室壁运动、心功能指标,术后3个月复查超声心动图检查评价室壁运动、心功能指标改善情况。③门控双核素心肌灌注/代谢显像(18F-FDG-SPECT)评价采用5分法:正常0分,稀疏1分,明显稀疏2分,缺损3分。超声心动图评价标准:正常1分,减低2分,明显减低3分,室壁无运动或矛盾运动4分;室壁运动二个分值或二个分值以上为室壁运动改善。主要观察指标:①门控双核素心肌灌注/代谢显像(18F-FDG-SPECT)结果。②超声心动图随访观察患者干细胞移植前后梗死相关心肌节段评分及心功能指标。结果:20例患者全部进入结果分析。①门控双核素心肌灌注/代谢显像(18F-FDG-SPECT)结果:20例患者心肌灌注缺损面积治疗后较治疗前明显减少((33±15)%,(44±18)%,P<0.05);代谢缺损面积治疗后较治疗前明显减少((33±17)%,(43±21)%,P<0.05);治疗前共有199个节段血流灌注及糖代谢缺损匹配,判定为坏死心肌,治疗后79个节段血流灌注代谢明显改善,仍有120个节段血流灌注、糖代谢无明显改善(P<0.05)。⑥超声心动图结果:患者术后射血分数值术后显著大于术前[(53±8)%,(42±7)%,P<0.05]。结论:经冠状动脉途径植入人骨髓间充质干细胞治疗心肌梗死,方法简单易行,治疗后梗死面积明显减少,坏死区域心肌血流灌注、代谢改善,术前判定为无存活心肌节段术后明显减少,患者心功能得到改善。

Intracoronary transplantation of autologous bone marrow mesenchymal stem cells in the treatment of acute myocardial infarction: A 3-month follow-up on the therapeutic effect

BACKGROUND: The area of myocardial infarction is the determinative factor of acute myocardial infarction prognosis. Amelioration of blood transportation and replacement therapy can reduce infarction area. Bone marrow mesenchymal stem cells can differentiate into cardiovascular tissue and are easy to obtain. After cultured and expanded in vitro, they can become the ideal cells for cardiovascular replacement therapy.OBJECTIVE: To evaluate the therapeutic effect of intracoronary transplantation of bone marrow mesenchymal stem cells in the treatment of myocardial infarction. DESIGN: Self-control observation taking the patients as subjects.SETTING: Department of Cardiology, Department of Nuclear Medicine,Echocardiogram Room, Nanjing First Hospital Affiliated to Nanjing Medical University.PARTICIPANTS: Totally 20 patients with acute myocardial infarction who received the therapy of bone marrow mesenchymal stem cells transplantation in the Department of Cardiology, Nanjing First Hospital Affiliated to Nanjing Medical University during March 2003 to March 2004 were recurited. Informed consents were obtained from the patients, and the complete postoperative follow up was over 3 months. The patients include 15 male and 5 female, and they were aged (64±10) years.METHODS: All the patients underwent percutaneous coronary intervention (PCI) to treat infarction-related blood vessel. Autologous bone marrow was taken from the patients, then stem cells were extracted to be performed in vitro induction, differentiation and proliferation, and transplanted infarction-related blood vessel through coronary artery at the mean number of (21.7±30.14)× 107 within 2 weeks. Before and 3 months after transplantation of stem cells, patients underwent gated dual-isotopic myocardial perfusion/metabolic imaging (18-fluoro-2-deoxy-glucose, 18F-FDG) examination. Survived and necrotic myocardia were predicted and infarction area was obtained. At the same time, wall motion and heart function index were evaluated with ultrasound cardiography (UCG)examination, and they were re-checked 3 months after operation to evaluate the amelioration of wall motion and heart function index. A 5-point scale was used in the evaluation of gated dual-isotopic myocardial perfusion/metabolic imaging (18F-FDG) examination: point 0: normal, 1: sparse, 2:obviously sparse, 3: defected. Evaluative standard of UCG: point 1: normal,2: reduced, 3: obviously reduced, 4: no ventricular wall motion or paradoxical motion; Wall motion with 2 points or more than 2 points suggests it is improved.MAIN OUTCOME MEASURES: ① Results of gated dual-isotopic myocardial perfusion/ metabolic imaging (18F-FDG-SPECT); ②Infarctionrelated myocardial segment score and heart function index before and after stem cell transplantation of patients in ECG follow-up observation.RESULTS: All the 20 patients participated in the result analysis.Results of gated dual-isotopic myocardial perrusion/metabolic imaging (18F-FDG-SPECT): The myocardial perfusion defect area of 20 patients was significantly reduced after therapy than before therapy [(33±15)%,-(44±18)% ,P ＜ 0.05]; Metabolie defect area was significantly reduced after therapy than before therapy [(33±17)%, (43±21)% ,P ＜ 0.05];Before therapy, there were 199 segments, in which blood flow reperfusion was matched to glycometabolism defect, and they were determined as necrotic myocardium. After therapy, blood flow perfusion metabolism was improved in 79 segments, but blood flow perfusion and glycometabolism were not improved significantly in 120 segments (P ＜ 0.05). Results of UCG: ejection fraction of patients was significantly larger after therapy than before therapy [(53±8)%, (42±7)% ,P ＜ 0.05].CONCLUSION: Intracoronary transplantation of human bone marrow mesenchymal stem cells for treating myocardial infarction is simple to operate. After therapy, the infarction area is obviously reduced, myocardial blood flow perfusion and metabolism of necrotic area improve, myocardial segments without survival determined before operation reduce sigrificantly and the heart function of patients improve.