Multimodal Magnetic Resonance and Fluorescence Imaging of the Induced Pluripotent Stem Cell Transplantation in the Brain

Abstract BackgroundThe understanding of the engrafted cell behaviors such as the survival, growth and distribution is the prerequisite to optimize cell therapy, and a multimodal imaging at both anatomical and molecular levels is designed to achieve this goal. Methods and results We constructed a lentiviral vector carrying ferritin heavy chain 1 (FTH1), near-infrared fluorescent protein (iRFP) and enhanced green fluorescent protein (EGFP) via T2A linker, and established the induced pluripotent stem cells (iPSCs) culture stably expressing these three reporter genes. These iPSCs showed green and near-infrared fluorescence as well as the iron uptake capacity in vitro. After transplanted the labeled iPSCs into the rat brain, the engrafted cells could be in vivo imaged using magnetic resonance imaging (MRI) and near-infrared fluorescent imaging (NIF) up to 60 days at the anatomical level, moreover, these cells could be detected using EGFP immunostaining and Prussian blue stain at the cellular level. Conclusions Our study provides a novel tool to study the cellular behaviors of the transplanted cells in a multimodal way, which will be valuable for the effectiveness and safety evaluation of cell therapy.