A strategy of retrograde injection of bone marrow mononuclear cells into the myocardium for the treatment of ischemic heart disease
A strategy of retrograde injection of bone marrow mononuclear cells into the myocardium for the treatment of ischemic heart disease
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DOI：
10.1016/j.yjmcc.2005.06.008
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发表时间：
2006-01-01
影响因子：
5
通讯作者：
Murohara, T
中科院分区：
文献类型：
--
作者：
Yokoyama, S;Fukuda, N;Murohara, T
目标。-据报道，骨髓细胞移植(BMI)能有效改善缺血性心脏病。然而，BMI策略通常是侵入性的。为了建立一种治疗缺血性心脏病的BMI策略，我们对急性心肌梗死(AMI)和陈旧性心肌梗死(OMI)的猪进行了自体骨髓冷冻保存的单个核细胞(MNC)经冠状静脉逆行植入心肌的实验。-BM细胞是从猪的烟熏中提取的。采用离心法收集单个核细胞，进行超低温保存。冠状动脉左前降支中段闭塞造成前壁心肌梗死，无需手术干预。心肌梗死诱导后6h和2周，冰冻的骨髓细胞快速解冻，经冠状静脉逆行注入心肌内，经单个球囊输注导管。术后4周行冠状动脉造影，用电导导管分析C心功能，激光共聚焦显微镜进行组织病理学分析。BMI后测定血浆利钠肽和血管生长因子水平。-流式细胞仪分析表明，90%的冻存BM细胞在体外是存活的。标记的BM细胞完全分布于猪的五味子核梗死区。BMI增加了梗塞心脏的侧支血管新生。BMI显著改善了AMI合并BMI和OMI合并BMI组的心功能。BMI还增加了梗死心脏微血管的形成。BMI后血浆利钠肽水平显著降低，血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(FGF2)水平显著升高。激光共聚焦显微镜显示BMI后梗死区存在心肌细胞的增殖和活化。-将深低温保存的BM细胞逆行注入心肌，有效地诱导了血管生成，并改善了急性心肌梗死或陈旧性心肌梗死猪的心功能。这些结果表明，目前的BMI策略将是安全和可行的，作为一种血管生成细胞治疗缺血性心脏病。(C)2005爱思唯尔有限公司。保留所有权利。
Objective. - Bone marrow cells implantation (BMI) has been reported to efficiently improve ischemic heart disease. However, BMI strategies are generally invasive. To establish a BMI strategy for ischemic heart disease, we performed implantation of autologous cryopreserved mononuclear cells (MNCs) from bone marrow (BM) retrogradely into the myocardium via the coronary vein in pigs with acute myocardial infarction (AMI) and old myocardial infarction (OMI).Methods. - BM cells were harvested from the pigs' fumurs. MNCs were collected by centrifugation and were cryopreserved. Anterior myocardial infarction was induced by occlusion of the midportion of the left anterior descending coronary artery without surgical intervention. Frozen BM cells were quickly thawed and injected retrogradely via the coronary vein into the myocardium through a single balloon infusion catheter 6 h and 2 weeks after the induction of infarction. Four weeks after implantation, coronary arteriograms were obtained, C cardiac function was analyzed with the use of a conductance catheter, and histopathologic anlysis was performed with a confocal laser microscope. Plasma levels of natriuretic peptides and angiogenic growth factors were measured after BMI.Results. - Flow cytometric analysis revealed that 90% of cryopreserved BM cells were viable in vitro. Labeled BM cells were entirely distributed around in the infarcted area of maycardium in pigs. BMI increased collateral neovascuralization in infarcted hearts. BMI significantly improved cardiac function in AMI with BMI and OMI with BMI groups. BMI also increased the formation of microcapillary arteries in infarcted hearts. Levels of natriuretic peptides were significantly decreased, and levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) were significantly increased after BMI. Confocal laser microscopy revealed the presence of proliferative and activated myocardial cells in infarcted hearts after BMI.Conclusion. - The retrograde infusion of cryopreserved BM cells into myocardium efficiently induced angiogenesis and improved cardiac function in pigs with AMI or OMI. These results suggest that the present strategy of BMI will be safe and feasible as an angiogenic cell therapy for ischemic heart disease. (c) 2005 Elsevier Ltd. All rights reserved.