Mesenchymal Stem Cells Provide Better Results Than Hematopoietic Precursors for the Treatment of Myocardial Infarction

Mesenchymal Stem Cells Provide Better Results Than Hematopoietic Precursors for the Treatment of Myocardial Infarction
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DOI:
10.1016/j.jacc.2009.08.092
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发表时间:
2010-05-18
影响因子:
24
通讯作者:
Sepulveda, Pilar
Sepulveda, Pilar
中科院分区:
医学1区
文献类型:
--
作者:
Arminan, Ana;Gandia, Carolina;Sepulveda, Pilar

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目的比较人CD 34(+)造血干细胞和骨髓间充质干细胞(MSC)移植治疗永久性左冠状动脉结扎大鼠心肌梗死(MI)的效果。但是没有进行比较研究来阐明哪种治疗更有效地防止左心室(LV)重构。方法将人骨髓MSC或从脐带血中新鲜分离的CD 34(+)细胞注射到梗死裸大鼠的心肌内。采用超声心动图分析心功能。心室重塑通过组织组织学和电子显微镜进行评估,新形成的血管通过免疫组织化学进行定量。苏木精-伊红染色评价左室壁慢性局部炎性浸润。梗死组织的细胞凋亡进行了评估,通过末端脱氧核苷酸转移酶dUTP缺口末端labelingassay.ResultsBoth细胞类型诱导LV心功能的改善,并增加心肌组织和新生血管的组织细胞增殖。然而,MSC在减少梗死面积和预防心室重构方面更有效。瘢痕组织在CD 34组中为17.48 +/- 1.29%,在MSC组中为10.36 +/- 1.07%(MSC与CD 34相比p < 0.001)。此外,与MSC不同,CD 34(+)处理的动物在移植后4周左室壁出现局部炎性浸润,并持续存在。结论间充质干细胞可能比CD 34(+)细胞对梗死的愈合更有效。这项研究有助于阐明这些细胞类型在MI治疗过程中的作用机制。(J Am科尔心脏病学杂志2010;55:2244-53)(C)美国心脏病学会基金会2010年
ObjectivesThe purpose of this study was to compare the ability of human CD34(+) hematopoietic stem cells and bone marrow mesenchymal stem cells (MSC) to treat myocardial infarction (MI) in a model of permanent left descendent coronary artery (LDA) ligation in nude rats.BackgroundTransplantation of human CD34(+) cells and MSC has been proved to be effective in treating MI, but no comparative studies have been performed to elucidate which treatment prevents left ventricular (LV) remodelling more efficiently.MethodsHuman bone marrow MSC or freshly isolated CD34(+) cells from umbilical cord blood were injected intramyocardially in infarcted nude rats. Cardiac function was analyzed by echocardiography. Ventricular remodelling was evaluated by tissue histology and electron microscopy, and neo-formed vessels were quantified by immunohistochemistry. Chronic local inflammatory infiltrates were evaluated in LV wall by hematoxylin-eosin staining. Apoptosis of infarcted tissue was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay.ResultsBoth cell types induced an improvement in LV cardiac function and increased tissue cell proliferation in myocardial tissue and neoangiogenesis. However, MSC were more effective for the reduction of infarct size and prevention of ventricular remodelling. Scar tissue was 17.48 +/- 1.29% in the CD34 group and 10.36 +/- 1.07% in the MSC group (p < 0.001 in MSC vs. CD34). Moreover, unlike MSC, CD34(+)-treated animals showed local inflammatory infiltrates in LV wall that persisted 4 weeks after transplantation.ConclusionsMesenchymal stem cells might be more effective than CD34(+) cells for the healing of the infarct. This study contributes to elucidate the mechanisms by which these cell types operate in the course of MI treatment. (J Am Coll Cardiol 2010;55:2244-53) (C) 2010 by the American College of Cardiology Foundation