CT/Bioluminescence Dual-Modal Imaging Tracking of Mesenchymal Stem Cells in Pulmonary Fibrosis

Abstract

Human mesenchymal stem cells (hMSCs), due to their immune regulation and collateral secretion effects, are currently explored for potential therapy of idiopathic pulmonary fibrosis (IPF). Understanding the migration, homing, functions, and survival of transplanted hMSCs in vivo is critical to successful IPF treatment. Therefore, it is highly desired to develop noninvasive and effective imaging technologies to track the transplanted hMSCs, providing experimental basis for improving the efficacy of hMSCs in the treatment of IPF. The rational design and development of a dual-labeling strategy are reported by integrating gold nanoparticle (AuNP)-based computed tomography (CT) nanotracers and red-emitting firefly luciferase (RfLuc)-based bioluminescence (BL) tags for CT/BL multimodal imaging tracking of the transplanted hMSCs in a murine model of IPF. In this approach, the CT nanotracer is prepared by sequential coupling of AuNPs with polyethylene glycol and trans-activator of transcription (TAT) peptide (Au@TAT), and employed it to monitor the location and distribution of the transplanted hMSCs in vivo by CT imaging, while RfLuc is used to monitor hMSCs viability by BLI. This facile strategy allows for visualization of the transplanted hMSCs in vivo, thereby enabling profound understanding of the role of hMSCs in the IPF treatment, and advancing stem cell-based regenerative medicine.

Keywords: CT imaging; bioluminescence imaging; gold nanotracers; idiopathic pulmonary fibrosis; stem cell tracking.