In vivo functional and transcriptional profiling of bone marrow stem cells after transplantation into ischemic myocardium.
In vivo functional and transcriptional profiling of bone marrow stem cells after transplantation into ischemic myocardium.
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骨髓干细胞移植到缺血心肌后的体内功能和转录谱。
DOI：
10.1161/atvbaha.111.238618
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Wu JC
中科院分区：
文献类型：
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作者：
Sheikh AY;Huber BC;Narsinh KH;Spin JM;van der Bogt K;de Almeida PE;Ransohoff KJ;Kraft DL;Fajardo G;Ardigo D;Ransohoff J;Bernstein D;Fischbein MP;Robbins RC;Wu JC
骨髓干细胞治疗心脏的临床试验产生了不同的结果。其潜在疗效的基本机制(S)仍不清楚。在本研究中，我们评估了心肌内骨髓单个核细胞(BMMC)移植在小鼠心肌梗死模型中用于心脏修复的存活动力学、转录反应和功能结果。我们利用分子遗传生物发光成像和高通量转录图谱来评价移植的骨髓单个核细胞植入缺血心肌后在体内的存活动力学和基因表达的变化。我们的结果表明细胞在移植后存活时间很短，只有不到1%的细胞在移植后6周存活。此外，对BMMCs的转录分析显示，各种细胞调控基因非特异性上调，而细胞分化和成熟途径明显下调。根据超声心动图、有创血流动力学和正电子发射断层扫描(PET)的评估，BMMC治疗引起的心功能改善有限。对细胞命运的组织学评估进一步证实了体内细胞跟踪和转录分析的结果。总而言之，这些数据表明，在目前的迭代中，BMMC疗法可能没有以前认为的那么有效。应考虑对现有细胞递送方案进行进一步改进，以获得更好的治疗效果。
Clinical trials of bone marrow-derived stem cell therapy for the heart have yielded variable results. The basic mechanism(s) that underlie their potential efficacy remains unknown. In the present study, we evaluate the survival kinetics, transcriptional response, and functional outcome of intramyocardial bone marrow mononuclear cell (BMMC) transplantation for cardiac repair in murine myocardial infarction model. We utilized molecular-genetic bioluminescence imaging and high throughput transcriptional profiling to evaluate the in vivo survival kinetics and gene expression changes of transplanted BMMCs after their engraftment into ischemic myocardium. Our results demonstrate short-lived survival of cells following transplant, with less than 1% of cells surviving by 6 weeks post-transplantation. Moreover, transcriptomic analysis of BMMCs revealed non-specific upregulation of various cell regulatory genes with a marked downregulation of cell differentiation and maturation pathways. BMMC therapy caused limited improvement of heart function as assessed by echocardiography, invasive hemodynamics, and positron emission tomography (PET). Histological evaluation of cell fate further confirmed findings of the in vivo cell tracking and transcriptomic analysis. Collectively, these data suggest that BMMC therapy, in its present iteration, may be less efficacious than once thought. Additional refinement of existing cell delivery protocols should be considered to induce better therapeutic efficacy.