Detailed analysis of bone marrow from patients with ischemic heart disease and left ventricular dysfunction: BM CD34, CD11b, and clonogenic capacity as biomarkers for clinical outcomes.
Detailed analysis of bone marrow from patients with ischemic heart disease and left ventricular dysfunction: BM CD34, CD11b, and clonogenic capacity as biomarkers for clinical outcomes.
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DOI：
10.1161/circresaha.115.304353
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发表时间：
2014-10-24
影响因子：
20.1
通讯作者：
Cardiovascular Cell Therapy Research Network (CCTRN)
中科院分区：
文献类型：
--
作者：
Cogle CR;Wise E;Meacham AM;Zierold C;Traverse JH;Henry TD;Perin EC;Willerson JT;Ellis SG;Carlson M;Zhao DX;Bolli R;Cooke JP;Anwaruddin S;Bhatnagar A;da Graca Cabreira-Hansen M;Grant MB;Lai D;Moyé L;Ebert RF;Olson RE;Sayre SL;Schulman IH;Bosse RC;Scott EW;Simari RD;Pepine CJ;Taylor DA;Cardiovascular Cell Therapy Research Network (CCTRN)
骨髓(BM)细胞治疗缺血性心脏病(IHD)的结果好坏参半。在充分发挥骨髓细胞治疗的作用之前，了解急性心肌梗死(AMI)后的骨髓生态位是非常必要的。目的：研究IHD合并严重左心功能不全(LVD)患者的骨髓成分。采用流式细胞仪和集落试验对280例IHD和LVD患者的骨髓进行了细胞亚群分析。急性心肌梗死后7天骨髓CD34+细胞百分比下降(平均值为1.9%，其他队列为2.3-2.7%；p<；0.05)。骨髓来源的内皮细胞集落显著减少(p<；0.05)。骨髓CD11b+细胞的增加与急性心肌梗死后左室射血分数(LVEF)的恶化有关(p<；0.05)。急性心肌梗死患者骨髓CD34+百分率升高与左心室射血分数明显改善(+9.9%比+2.3%，p=0.03；慢性肾功能不全患者+6.6%比-0.02%，p=0.021)，慢性心肌病患者骨髓CD34+百分率下降与细胞治疗后左心室射血分数下降(-2.9%比+0.7%，p=0.0355)相关。在这项研究中，我们发现骨髓细胞亚群的异质性混合，内皮细胞集落容量降低，CD34+细胞在急性心肌梗死后7天内降至最低点，CD11b百分比与梗死后LVEF呈负相关，CD34百分比与细胞治疗后LVEF的变化呈正相关。这些结果可能是在自体骨髓细胞治疗试验中看到的微小临床改善的基础，并支持选择有效的细胞亚群和/或逆转共病骨髓损害。
Bone marrow (BM) cell therapy for ischemic heart disease (IHD) has shown mixed results. Before the full potency of BM cell therapy can be realized, it is essential to understand the BM niche following acute myocardial infarction (AMI). To study the BM composition in patients with IHD and severe left ventricular dysfunction (LVD). BM from 280 patients with IHD and LVD were analyzed for cell subsets by flow cytometry and colony assays. BM CD34+ cell percentage was decreased 7 days after AMI (mean of 1.9% vs. 2.3-2.7% in other cohorts; p< 0.05). BM-derived endothelial colonies were significantly decreased (p< 0.05). Increased BM CD11b+ cells associated with worse left ventricular ejection fraction (LVEF) after AMI (p< 0.05). While increased BM CD34+ percentage associated with greater improvement in LVEF (+9.9% vs. +2.3%, p=0.03, for AMI patients; and +6.6% vs. -0.02%, p=0.021 for chronic IHD patients), decreased BM CD34+ percentage in chronic IHD patients correlated with decrement in LVEF after cell therapy (-2.9% vs. +0.7%, p=0.0355). In this study we show a heterogeneous mixture of BM cell subsets, decreased endothelial colony capacity, a CD34+ cell nadir seven days after AMI, a negative correlation between CD11b percentage and post-infarct LVEF, and positive correlation of CD34 percentage with change in LVEF after cell therapy. These results serve as a possible basis for the small clinical improvement seen in autologous BM cell therapy trials and support selection of potent cell subsets and/or reversal of co-morbid BM impairment.