Transplantation of autologous fresh bone marrow into infarcted myocardium:: A word of caution
Transplantation of autologous fresh bone marrow into infarcted myocardium:: A word of caution
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DOI：
10.1161/01.cir.0000089040.11131.d4
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发表时间：
2003-09-09
期刊：
影响因子：
37.8
通讯作者：
Menasché, P
中科院分区：
文献类型：
--
作者：
Bel, A;Messas, E;Menasché, P
背景-由于新鲜（未分割的）自体骨髓（BM）的临时移植（Tx）的益处已在急性心肌梗塞的情况下进行了初步研究，我们评估了这种方法是否可以有效地再生慢性梗塞的心肌。方法和结果-通过结扎回旋动脉分支在18只羊中产生心肌梗塞。三周后，从髂嵴吸出BM，清洗，用荧光染料Dil标记，并通过重新开胸术在梗塞区域的10个部位重新注射（平均：3 mL中的422x10（6）个细胞）（n = 9）。九个对照接受培养基。在 Tx 之前和 Tx 后 2 个月通过二维超声心动图评估左心室 (LV) 功能，而使用 M 型组织多普勒成像在梗塞/移植区域中心测量透壁速度梯度。对福尔马林固定的心脏进行处理以检测移植细胞和血管生成。 Tx 组和对照组的 LV 射血分数恶化程度相似（分别从 42+/-5% 降至 30+/-4% 和从 40+/-4% 降至 31+/-1%；P=0.86）。同样，BM Tx 未能防止左心室扩张和整体室壁运动评分受损。区域收缩速度梯度 (s(-1)) 的下降具有类似的模式（Tx 组：从 0.77+/-0.11 到 0.31+/-0.07；对照组：从 0.73+/-0.10 到 0.50+/-0.07；P=0.06）。组织学上，除了梗死纤维化区域中的一些分散的 Dil 阳性巨噬细胞外，既没有 BM 组织植入，也没有 BM 细胞转分化为内皮细胞。结论 - 这些数据警告人们不要将新鲜未分割的 BM 临时 Tx 转化为梗死后疤痕的功能功效。
Background-As the benefits of extemporaneous transplantation (Tx) of fresh (unfractionated) autologous bone marrow (BM) have been primarily studied in the setting of acute myocardial infarction, we assessed whether this approach could be effective for regenerating chronically infarcted myocardium.Methods and Results-Myocardial infarction was created in 18 sheep by ligation of circumflex arterial branches. Three weeks later, BM was aspirated from the iliac crest, washed, labeled with the fluorescent dye Dil and reinjected (mean: 422x10(6) cells in 3 mL) in 10 sites across the infarcted area through the reopened thoracotomy (n=9). Nine controls received culture medium. Left ventricular (LV) function was assessed before and 2 months after Tx by two-dimensional echocardiography whereas transmural velocity gradients were measured using M-mode tissue Doppler imaging at the center of the infarcted/grafted area. Formalin-fixed hearts were processed for the detection of grafted cells and angiogenesis. LV ejection fraction deteriorated similarly in the Tx and control groups (from 42+/-5% to 30+/-4% and from 40+/-4% to 31+/-1%, respectively; P=0.86). Likewise, BM Tx failed to prevent LV dilatation and impairment of the global wall motion score. The decrease in regional systolic velocity gradients (s(-1)) featured a similar pattern (Tx group: from 0.77+/-0.11 to 0.31+/-0.07; control group: from 0.73+/-0.10 to 0.50+/-0.07; P=0.06). Histologically, there was neither BM tissue engraftment, except for a few scattered Dil-positive macrophages in the infarcted fibrotic areas nor transdifferentiation of BM cells into endothelial cells.Conclusion-These data caution against the functional efficacy of extemporaneous Tx of fresh unfractionated BM into postinfarction scars.