摘要
心肌梗死(MI)后心脏组织的修复能力减弱。骨髓间充质干细胞(BMSCs)已被有效地用于治疗心肌梗死后受损组织。缺氧诱导因子(HIF-1α)能诱导大量的促血管生成相关基因的转录并增强干细胞的生存力。在这里,我们研究的是HIF-1α-转换的BMSCs是否可增强在心肌梗死后组织修复的能力,比较微型PET/CT和超声心动图检查评价治疗效果的价值。大鼠骨髓间充质干细胞表达HIF-1α和NIS(lenti-hif-1α-NIS)的慢病毒转导。钠碘转运体(NIS)作为有效报告基因的功能,允许BMSCs移植到大鼠心脏长达2周并使用微SPECT/CT成像。在大鼠心肌梗死模型中,对HIF-1α-NIS-转换的BMSCs移植后心肌梗死区,更多关于HIF-1α、VEGF和Ang-4基因的表达,新陈代谢的改善,在心肌梗死区,肝纤维化组织及心肌细胞凋亡更少的被检测到。此外,我们发现大多数移植的HIF-1α-NIS转导骨髓间充质干细胞分化为内皮细胞,并在心肌梗死区产生新生血管。代谢活性在早期时间点显著升高(术后2周),并持续增加(4周),由18F-FDG微PET/CT吸收成像所示。超声心动图显示心脏功能在2周无改善,在4周时有细微改善。这项研究表明,18F-FDG 微PET/CT在评价早期疗效方面优于超声心动图。
关键词: 细胞治疗,基因治疗,分子影像学,心肌梗死.
Current Gene Therapy
Title:Molecular Imaging to Monitor Repair of Myocardial Infarction Using Genetically Engineered Bone Marrow-Derived Mesenchymal Stem Cells
Volume: 15 Issue: 5
Author(s): Shuo Shi, Min Zhang, Rui Guo, Xiangming Zhang and Biao Li
Affiliation:
关键词: 细胞治疗,基因治疗,分子影像学,心肌梗死.
摘要: Heart tissue has a diminished ability to repair after myocardial infarction (MI). Bone marrow- derived mesenchymal stem cells (BMSCs) have been used effectively to heal damaged tissue after MI. Hypoxia-inducible factor-1α (HIF-1α) can induce transcription of numerous pro-angiogenic genes and enhance stem cell survival. Here, we investigated whether HIF-1α-transduced BMSCs could enhance tissue repair after MI, and compared the value of micro-PET/CT and echocardiography for evaluation of therapeutic effects. Rat BMSCs were transduced with a lentivirus expressing HIF-1α and NIS (Lenti-HIF-1α-NIS). Sodium iodide symporter (NIS) functioned as effective reporter gene, allowing monitoring of BMSCs transplanted into the rat heart for up to 2 weeks using micro-SPECT/CT imaging. In a rat MI model, after transplantation of HIF-1α-NIS-transduced BMSCs to the MI zone, more expression of HIF-1α,VEGF and Ang-4, more improvement of metabolism, less fibrotic tissue and cardiomyocyte apoptosis were detected in the MI zone. Moreover, we found that most of the transplanted HIF-1α-NIS-transduced BMSCs differentiated into endothelial cells, and engineered new blood vessels in MI zone. Metabolic activity significantly increased at an early time point (2 weeks after transplantation) and lead to a sustained increase (4 weeks), as indicated by 18F-FDG uptake in micro-PET/CT imaging. Echocardiography indicated no improvement in cardiac function at 2 weeks and small improvement at 4 weeks. This study indicated that 18F-FDG micro-PET/CT was more useful for evaluating early therapeutic effects than echocardiography.
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Shi Shuo, Zhang Min, Guo Rui, Zhang Xiangming and Li Biao, Molecular Imaging to Monitor Repair of Myocardial Infarction Using Genetically Engineered Bone Marrow-Derived Mesenchymal Stem Cells, Current Gene Therapy 2015; 15 (5) . https://dx.doi.org/10.2174/1566523215999150421164034
DOI https://dx.doi.org/10.2174/1566523215999150421164034 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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