中文摘要
T2WI本底模糊效应以及无法判断纳米铁颗粒是否位于移植细胞内是超顺磁性氧化铁(SPIO/USPIO)作为细胞标记物MR示踪研究的缺陷。我们前期研究新型T1阳性纳米铁VSOP时发现,VSOP能够克服传统纳米铁的“开花效应”,同时VSOP-PEI作为新型基因导入载体在转染效率方面优于传统方法,有望成为新的分子探针。本研究拟利用VSOP纳米基因载体转染激活的M2型巨噬细胞,干预miR-21表达,调控相关靶基因参与心脏结构重构,通过VSOP-PEI-FI双模态探针标记细胞移植于兔梗死心肌,活体评价VSOP示踪移植细胞的可行性,分析标记细胞导致磁共振信号的演变及其组织学和分子生物学基础;利用双荧光显像判断移植细胞的存活状态,动态评估巨噬细胞移植对心肌梗死后瘢痕修复的效果,对巨噬细胞在心肌梗死后细胞外基质修复及左室重塑的可能机制进行探讨,旨在为心肌梗死后细胞移植提供新的靶点与监测方法。
英文摘要
MRI tracing SPIO labeled transplanted cells is a research focus of molecular imaging, but there are defects such as T2WI background blurring effect and failure to judge which cells SPIO nanoparticles were located in according to MR signal. In our preliminary studies, a new T1 positive iron oxide particles VSOP were used in MR imaging of labeled cell, it has been found that VSOP could overcome the “blooming effect” of SPIO/USPIO contrast agent on T2WI sequence and have potential to be new probe for cell imaging.This research intends to explore the feasibility of VSOP-EPI transfection of activated M2 macrophages in miR-21 expression comparing with lipofection, and regulate apoptosis or proliferation-related target genes in the occurrence and development of cardiac structural remodeling. In addition, the feasibility of VSOP tracing transplanted cells is evaluated in vivo by transplantation VSOP-PEI-FI labeled M2 macrophages to infarcted myocardium of rabbits. The evolution of the MR signal by the marked macrophages is observed and the histology and molecular biology bases of MR signal are explored. Meanwhile, we will estimate the survival of the transplanted cells by double fluorescence staining of macrophages, observe the differentiation and inflammatory cytokine secretion, dynamically assesses the role of transplanting macrophages after myocardial infarction in the extracellular matrix recovery and left ventricular remodeling. The purpose of this study is to providing new target site and monitoring method for cell transplantation in myocardial infarction.
