课题背景：课题为江苏省“135”重点人才培养项目（RC2003092）子课题及无锡市社会发展指令性项目(CS04--0001)。课题研究将自体骨髓干细胞应用于并发心力衰竭的扩张性心肌病、冠状动脉粥样硬化性心脏病和风湿性二尖瓣患者，取得了较满意的临床效果，拓展了骨髓干细胞移植的应用领域，为缺乏供体的扩张性心肌病患者提供了新的治疗手段，其临床应用范围的扩大带来了巨大的社会和经济效益。

应用要点：①在科研设计上，拓展了骨髓干细胞移植的应用领域，尤其将骨髓干细胞移植辅助应用于瓣膜疾病的外科治疗和扩张性心肌病等待心脏移植时的过渡治疗。②在心功能的评价手段上，将核素显像技术应用于干细胞移植前后的冠状动脉粥样硬化性心脏病患者，结果更精确可靠。③在移植方式上，用于瓣膜疾病并发心力衰竭患者外科辅助治疗时，将骨髓干细胞悬液自左、右冠状动脉和心肌内注射，每个心肌注射点相距2 cm，注射点用生物蛋白胶封闭。

偏倚或不足：①入选病例较少，随访时间较短，远期效果有待于临床进一步验证。②对心功能的评价指标过于单一，有必要进一步丰富心功能评价指标，以更精确评价治疗效果。③下一步拟在并发心力衰竭的瓣膜病患者术前行干细胞移植，扩大此类患者的手术指征。

摘要
目的：心肌细胞在人类出生后已几乎失去增殖能力，增加具有完整收缩功能的心肌细胞数目是治疗心力衰竭所致心肌损伤的关键。实验拟进一步观察和验证自体骨髓干细胞移植对心力衰竭患者近期心功能的影响。
方法：①对象：选取2003-10/2005-06苏州大学附属第四医院胸心外科收治的23例急性心肌梗死患者，随机数字表法分为心肌梗死细胞移植组7例，心肌梗死对照组16例。另选取2003-10/2005-06收治的11例严重风湿性心脏病、二尖瓣狭窄合并全心衰竭女性患者为二尖瓣病变细胞移植组，以2001-10/2003-10收治的同类疾病女性患者10例为二尖瓣病变瓣膜置换组。以上4组患者术前均依靠大剂量正性肌力药物和利尿剂维持心功能，患者及其家属对治疗均签署知情同意书，实验经医院医学伦理委员会批准。②实验方法：无菌条件下在髂前上棘抽取骨髓25 mL，用DMEM完全培养基分离培养骨髓干细胞，贴壁筛选法进行纯化的。细胞达80%融合时用胰酶消化传代，取第3代细胞用于移植，浓度调整为1.5×1010 L-1。心肌梗死细胞移植组将自体骨髓干细胞悬液自左、右冠状动脉注入5 mL。心肌梗死对照组患者仅行常规治疗。二尖瓣病变细胞移植组患者在二尖瓣置换术中将自体骨髓干细胞悬液自左、右冠状动脉注入，同时行心肌内注射，每点注射0.1~0.2 mL，间距2 cm，注入量共5 mL。二尖瓣病变瓣膜置换组单纯行二尖瓣置换术。③实验评估：细胞移植前后通过心脏超声以及核素显像方法全面评价心功能。
结果：4组患者均完成3个月随访。①自体骨髓干细胞移植对急性心肌梗死心功能的影响：与心肌梗死对照组比较，术前 10 d及术后2周心肌梗死细胞移植组射血分数、心输出量、心肌梗死面积均基本相似（P > 0.05）；术后4，6，8周射血分数、心输出量均显著提高（P < 0.01），心肌梗死面积均显著缩小（P < 0.01）。②自体骨髓干细胞移植对风湿性二尖瓣病变心功能的影响：与二尖瓣病变瓣膜置换组比较，二尖瓣病变细胞移植组术后4周射血分数和心输出量均明显提高(t =3.97，P < 0.01；t = 3.61，P < 0.01) ，至术后8周差异最为明显，提高效果均显著优于术后4周（t =2.91，P < 0.05；t=2.64，P < 0.05）。
结论：自体骨髓干细胞移植可明显改善冠状动脉粥样硬化性心脏病心肌梗死患者的心功能，辅助用于风湿性二尖瓣并发心力衰竭患者的外科治疗亦能对心功能有所提高。
关键词：骨髓间充质干细胞；移植，自体；心力衰竭

游庆军，沈振亚，肖明第，蒋锡初.自体骨髓干细胞移植对心力衰竭患者近期心功能的影响[J].中国组织工程研究与临床康复，2008，12(8):1467-1471 [www.zglckf.com/zglckf/ejournal/upfiles/08-8/8k-1467(ps).pdf]

Influence of autologous bone marrow stem cell transplantation on short-term heart function in cardiac failure patients

Abstract

AIM：The myocardial cells lost their ability of proliferation when human being is born. Current researches have focused on how to treat heart failure by supplying functional myocardial cells. This study showed the effect of mesenchymal stem cell transplantation on late heart function in patients with heart failure.

METHODS: ①From October 2003 to June 2005, 23 patients with acute myocardial infarction were admitted at the Department of Cardiothoracic Surgery, Fourth Hospital, Soochow University into two groups randomly. 7 patients in experimental group were received bone marrow stem cell transplantation, while 16 patients in control group only cured with traditional way. At the same time, we took another 11 patients with severe rheumatic heart disease, severe bicuspid valve disease and heart failure into experimental group, and patients in experimental group were treated with bone marrow stem cell transplantation during the surgery of bicuspid valve replacement. Divided another 10 patients treated in the last 2 years with severe bicuspid valve disease and heart failure into control group, patients in control group were only performed bicuspid valve replacement. Above-mentioned patients received inotropic agent and diuretic agent to maintain heart function. Patients and their family members singed informed consents. The study was approved by Hospital Medical Ethics Committee. ② Bone marrow (25 mL) was aseptically collected from anterosuperior iliac spine. Bone marrow stem cells were generally taken from bone marrow，isolated and cultivated in DMEM medium. Cells of 80% confluence were passaged by trypsinization. Three passage of cells were used for transplantation at 1.5×1010 L-1. In experimental myocardial infarction group, we perfused 5 mL mesenchymal stem cells into the heart by coronary artery. Patients in the control myocardial infarction group only received routine therapy. While in experimental bicuspid valve disease group, 5 mL mesenchymal stem cells were perfused through coronary artery and injected into different parts of myocardium directly, 0.1-0.2 mL at each point, with an interval of 2 cm. Patients in the mitral lesion control group received replacement of mitral valve. ③Heart function was assessed by ultrasonic cardiography and radionuclide imaging.

RESULTS: All patients were followed up for 3 months. ①Compared to the control group, patients in experimental myocardial infarction group got significant improvement in cardiac output (CO), ejection fraction (EF) and myocardial infarct size 10 days before the surgery and 2 weeks after the surgery (P > 0.05). EF and CO were significantly elevated at week 4, 6 and 8 after the surgery (P < 0.01), and myocardial infarct size was shortened (P < 0.01). ②Compared to the control group, EF and CO were significantly elevated at week 4 after the surgery in the experimental bicuspid valve disease group (t =3.97，P < 0.01；t =3.61，P < 0.01), and significantly at week 8 （t =2.91，P < 0.05；t =2.64，P < 0.05）.

CONCLUSION: Autologous bone marrow stem cell transplantation can improve heart function of patients with coronary atherosclerotic heart disease heart failure, so does in patients with rheumatic mitral valve and cardiac failure.

You QJ, Shen ZY, Xiao MD, Jiang XC.Influence of autologous bone marrow stem cell transplantation on short-term heart function in cardiac failure patients.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(8):1467-1471(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-8/8k-1467(ps).pdf]