骨髓细胞的分馏限制了非再灌注急性心肌梗死小鼠模型中的功能疗效。

Fractionation of mouse bone-marrow cells limits functional efficacy in non-reperfused mouse model of acute myocardial infarction.

机构信息

Division of Cardiology, Department of Medicine, University of California , San Francisco, San Francisco, CA, USA.

出版信息

Ann Med. 2012 Dec;44(8):829-35. doi: 10.3109/07853890.2012.672026. Epub 2012 Apr 12.

DOI:10.3109/07853890.2012.672026

PMID:22494088

Abstract

BACKGROUND AND OBJECTIVES

Clinical trials of bone-marrow (BM)-derived cells for therapy after acute myocardial infarct (MI) have been controversial. The most commonly used cells for these trials have been mononuclear cells (MNC), obtained by fractionation of BM cells (BMCs) via different protocols. In this study, we performed a head-to-head comparison of: 1) whole BMC; 2) fractionated BM (fBM) using the commonly used Ficoll protocol; 3) the extract derived from the fBM (fBM extract) versus 4) saline (HBSS) control for treatment of acute MI.

METHODS

In total, 155 male C57BL/6J (10-12-week old) mice were included. Echocardiography was performed at baseline and 2 days after permanent ligation of the left anterior descending artery to induce MI. Echocardiography and histology were employed to measure outcome at 28 days post-MI.

RESULTS

Whole BMC therapy improved left ventricular ejection fraction (LVEF) post-MI, but fBM or fBM extract was not beneficial compared to control (change of LVEF of 4.9% ±4.6% (P = 0.02), -0.4% ±5.8% (P = 0.86), -2.0% ±6.2% (P = 0.97) versus -1.4% ±5.3%, respectively). The histological infarct size or numbers of arterioles or capillaries at infarct or border zone did not differ between the groups.

CONCLUSIONS

Clinical studies should be performed to test whether whole BMC therapy translates into better outcome also after human MI.

摘要

背景和目的

骨髓（BM）来源的细胞在急性心肌梗死（MI）后的治疗临床试验一直存在争议。这些试验中最常使用的细胞是单核细胞（MNC），通过使用不同方案对 BM 细胞（BMCs）进行分离来获得。在这项研究中，我们对以下内容进行了直接比较：1）全 BMC；2）使用常用的 Ficoll 方案分离的 BM（fBM）；3）从 fBM 中提取的提取物（fBM 提取物）与 4）生理盐水（HBSS）对照用于治疗急性 MI。

方法

总共纳入了 155 只雄性 C57BL/6J（10-12 周龄）小鼠。在永久性结扎左前降支以诱导 MI 后，进行基线和 2 天的超声心动图检查。使用超声心动图和组织学来测量 MI 后 28 天的结果。

结果

全 BMC 治疗可改善 MI 后左心室射血分数（LVEF），但与对照组相比，fBM 或 fBM 提取物并无益处（LVEF 的变化分别为 4.9%±4.6%（P=0.02）、-0.4%±5.8%（P=0.86）、-2.0%±6.2%（P=0.97）与-1.4%±5.3%）。梗死或边界区的梗死大小或小动脉或毛细血管数量在各组之间没有差异。