课题背景：骨髓干细胞是具有自我复制和多向分化潜能的多能干细胞，可作为受损心肌组织修复的供体细胞。骨髓单个核细胞为一组多潜能干细胞的混合体，可能为心肌梗死区的组织再生和功能重建提供有效的治疗策略。课题为上海市卫生局科技发展基金资助项目（054065），主要从事骨髓单个核细胞移植治疗终末期心力衰竭的基础与临床研究，目前该课题进展顺利，已在国内核心期刊发表论著5篇。

应用要点：初步临床试验证实，骨髓干细胞移植有助于改善心肌梗死后近期左心室泵功能，而关于移植后远期疗效的临床报道较少。本课题选题密切结合临床热点,采用随机、对照、前瞻性的临床试验, 应用超声心动图评价心脏收缩功能和几何参数改变；血清氮末端脑钠素前体(NT-proBNP)测定间接评价心功能的改变；明尼苏达心衰问卷评价患者生活质量，旨在评价经冠状动脉自体骨髓单个核细胞移植治疗急性前壁心肌梗死的远期疗效，初步探讨了其内在机制。

偏倚或不足：样本量较小，骨髓单个核细胞移植对心肌梗死后心力衰竭的远期疗效仍不确定，尚无法阐明其确切机制。

摘要
目的：经冠状动脉自体骨髓单个核细胞移植有助于急性心肌梗死后左心室功能的恢复，但关于移植后远期疗效的临床报道较少。采用随机、对照、前瞻性的临床实验，随访12个月，评价经冠状动脉自体骨髓单个核细胞移植治疗急性前壁心肌梗死远期疗效。
方法：实验于2005-05/2006-09在复旦大学附属华山医院心导管室完成。①实验分组：入选华山医院心内科26例ST段抬高的急性前壁心肌梗死住院患者，随机分组：骨髓单个核细胞移植组(n=14)行经皮冠状动脉介入治疗联合经冠状动脉自体骨髓单个核细胞移植，经皮冠状动脉介入术当天，选取左髂后上棘为穿刺点行骨髓单个核细胞的分离纯化；对照组(n=12)仅接受经皮冠状动脉介入治疗。患者对治疗知情同意，治疗经医院伦理委员会批准。②实验评估：术后6，12个月，应用超声心动图评价心脏收缩功能和几何构型参数改变；应用电化学发光免疫学方法检测血清氮末端脑钠素前体水平，间接评价心功能的变化；明尼苏达心力衰竭问卷评价患者生活质量。
结果：①超声心动图显示，经冠状动脉自体骨髓单个核细胞移植6个月后，骨髓单个核细胞移植组左室射血分数明显升高 （P < 0.05），而随访至12个月时，移植组左室射血分数有进一步增加的趋势，但与6个月时比较则无统计学意义,心脏几何构型参数改变均无统计学意义。②骨髓单个核细胞移植术后6个月，骨髓单个核细胞移植组血清氮末端脑钠素前体水平明显降低（P=0.001）；而术后6个月与12个月比较, 血清氮末端脑钠素前体水平仍有进一步下降的趋势，但无统计学意义。③ 心力衰竭问卷评分提示，骨髓单个核细胞移植有利于急性前壁心肌梗死患者生活质量的改善。
结论：经冠状动脉自体骨髓单个核细胞移植治疗急性前壁心肌梗死，可以改善患者临床症状，由于样本量较小，对心肌梗死后心力衰竭的远期疗效仍然尚不确定。
关键词：心肌梗死；细胞移植；心肌再生；骨髓；血清氮末端脑钠素前体

金波，杨云贵，施海明，罗心平，李勇，孙宇立，李剑，沈伟.经冠状动脉自体骨髓单个核细胞移植治疗急性前壁心肌梗死：12个月疗效评价[J].中国组织工程研究与临床康复，2008，12(12):2267-2271
[www.zglckf.com/zglckf/ejournal/upfiles/08-12/12k-2267(ps).pdf]

Autologous intracoronary mononuclear bone marrow cell transplantation for acute anterior myocardial infarction: Outcomes after 12-month follow-up

Abstract

AIM：Intracoronary transplantation of autologous bone marrow mononuclear cells (BMMNCs) may enhance recovery of left ventricular function in patients after acute myocardial infarction（AMI）. However, little information is available about the long-term therapeutic potency of BMMNCs transplantation in AMI. We evaluated 12 months follow-up outcomes of acute anterior myocardial infarction by autologous BMMNCs transplantation in the prospective randomized controlled clinical trial.

METHODS: The experiments were performed at the Cardiovascular Laboratory of Huashan Hospital of Fudan University from May 2005 to September 2006. ①Twenty-six in-patients with acute anterior myocardial infarction were randomly included at the Department of Cardiology of Huashan Hospital. After percutaneous coronary intervention (PCI) for acute occlusion coronary artery, 14 patients were transplanted with autolougous BMMNCs via infarct-related coronary artery as transplantation group. BMMNCs were harvested and isolated from left posterior superior spine puncture before elective PCI. Another 12 patients were treated by percutaneous coronary intervention alone as control group. The study protocol was approved by the ethics committee of Huashan Hospital. All patients gave written informed consents. ②Six months and 12 months after BMMNCs transplantation, echocardiography was performed to evaluate the changes in cardiac function and geometric patterns again. The amino-terminal pro-brain natriuretic peptide (NT-proBNP) was measured by using electrochemiluminescence to evaluate the changes in cardiac function indirectly. Minnesota living with heart failure questionnaire was performed to evaluate the quality of life after intracoronary BMMNCs transplantation.

RESULTS:①Echocardiography: After 6 months of follow-up, left ventricular ejection fraction (LVEF) had increased significantly in transplantation group compared to the control group（P < 0.05）, while there was limited improvement and no statistical significance after 12 months. The changes in cardiac geometric patterns revealed no significantly recovery during 12 months follow-up. ② 6 months after BMMNCs transplantation, the serum NT-proBNP was decreased significantly compared to the control group（P=0.001）, while it did not change significantly after 12 months.③Minnesota living with heart failure (MLWHF) questionnaire indicated significantly improvement of life quality after transplantation compared to the control group.

CONCLUSION: Autologous intracoronary BMMNCs transplantation provides therapeutic efficacy after acute anterior myocardial infarction; however, the sustained benefit on heart failure after AMI remains uncertain because of the limitations of small sample size.

Jin B, Yang YG, Shi HM, Luo XP, Li Y, Sun YL, Li J, Shen W.Autologous intracoronary mononuclear bone marrow cell transplantation for acute anterior myocardial infarction: Outcomes after 12-month follow-up.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(12):2267-2271(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-12/12k-2267(ps).pdf]