利用基因工程化的骨髓间充质干细胞对心肌梗死的分子影像学监测

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.

Cite this article as:

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