分子影像学方法可以对移植细胞进行示踪，明确其在生物体内的行为特征，极大推动了再生医学的发展。传统分子成像基于单一影像手段，显像剂会随细胞增殖被稀释，无法长期追踪移植细胞。此外，显影剂在细胞凋亡后被免疫细胞吞噬而仍持续存在，影响对细胞存活情况的判断。鉴于传统方法的以上缺点，开发一种对移植细胞进行准确示踪且不受细胞凋亡影响的精准检测方法成为迫切需求。本研究拟开发同时表达三种不同成像报告基因的分子探针，可以同时在以下三种影像检查中成像： 1. 铁蛋白，MR上显影；2. GCaMP3荧光蛋白，荧光显微镜显影；3. 单纯疱疹病毒胸苷激-1，正电子发射体层成像。我们在验证其有效性和安全性的基础上，应用于猪心肌梗死干细胞治疗的活体动态观察中，明确整合影像报告基因的干细胞在猪心肌内的长期命运及发挥的心肌修复功能，并通过注射更昔洛韦诱导移植细胞死亡，揭示细胞治疗的潜在机制。

Progress in regenerative medicine will be accelerated by the Non-invasive molecular imaging characterizing the fate of cells after transplantation to host tissue by monitoring cell biological properties. Disadvantage of the traditional cell visualization approaches based on a single imaging technique is that the labeling agents are getting diluted along with cell divisions, and cannot be distinguished between live and dead cells. We plan to create a method of the dynamics imaging reporter cassette combining three reporters gene. This method can be used in different imaging modalities into one integrated toolkit. Specifically, 1) Ferritin, MRI; 2) GCaMP3, fluorescence; and 3) Herpes simplex virus thymidine kinase type 1（HSV1-tk）, positron emission tomography (PET). Based on the safety and functionality of our novel triple reporter in vitro, an immediate application for in vivo studies of transplantation of MSCs engineering with reporter gene after myocardial infarction for the longitudinal tracking the cell fate and evaluation of the heart regeneration capacity and reveal the underlying mechanism. HSV1-tk makes transgenic cells susceptible to killing via ganciclovir administration, which will provide valuable tool to reveal the underlying mechanism of cell therapy.