title: Molecular imaging to monitor repair of myocardial infarction using genetically engineered bone marrow-derived mesenchymal stem cells.
abstract: 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 (18)F-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 (18)F-FDG micro-PET/CT was more useful for evaluating early therapeutic effects than echocardiography.
authors.forename: Shuo
authors.initials: S
authors.lastname: Shi
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Ying
authors.initials: Y
authors.lastname: Miao
authors.forename: Xiangming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197, Ruijin Er Rd, Shanghai 200025, China. lb10363@rjh.com.cn.
authors.forename: Biao
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001853:Bone Marrow / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D005818:Genetic Engineering / Q000379:methods; D006321:Heart / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D057054:Molecular Imaging / Q000379:methods; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology; D000099209:Sodium-Iodide Symporters
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D027981:Symporters; D042461:Vascular Endothelial Growth Factor A; D000099209:Sodium-Iodide Symporters