Tracking Cell Viability for Adipose-Derived Mesenchymal Stem Cell-Based Therapy by Quantitative Fluorescence Imaging in the Second Near-Infrared Window

Abstract

Cell survival rate determines engraftment efficiency in adipose-derived mesenchymal stem cell (ADSC)-based regenerative medicine. In vivo monitoring of ADSC viability to achieve effective tissue regeneration is a major challenge for ADSC therapy. Here, we developed an activated near-infrared II (NIR-II) fluorescent nanoparticle consisting of lanthanide-based down-conversion nanoparticles (DCNPs) and IR786s (DCNP@IR786s) for cell labeling and real-time tracking of ADSC viability in vivo. In dying ADSCs due to excessive ROS generation, absorption competition-induced emission of IR786s was destroyed, which could turn on the NIR-II fluorescent intensity of DCNPs at 1550 nm by 808 nm laser excitation. In contrast, the NIR-II fluorescent intensity of DCNPs was stable at 1550 nm by 980 nm laser excitation. This ratiometric fluorescent signal was precise and sensitive for tracking ADSC viability in vivo. Significantly, the nanoparticle could be applied to quantitively evaluate stem cell viability in real-time in vivo. Using this method, we successfully sought two small molecules including glutathione and dexamethasone that could improve stem cell engraftment efficiency and enhance ADSC therapy in a liver fibrotic mouse model. Therefore, we provide a potential strategy for real-time in vivo quantitative tracking of stem cell viability in ADSC therapy.