Real-Time Imaging Tracking of Mesenchymal Stem Cells Labeled with Lipid-Poly(lactic-co-glycolic acid) Nanobubbles

Stem-cell-based therapy has attracted considerable attention due to the significant benefits to patients experiencing a wide range of diseases and injuries. However, their underlying mechanism of action is not completely understood. One main reason is the lack of imaging tools for real-time tracking of deep-seated transplanted stem cells. For the present study, we exploited a lipid poly(lactic-co-glycolic acid) nanobubble (LPN) probe with nanoscale size, good compatibility, and strong contrast-enhanced ultrasound signals. Due to the nanoscale particle size, cellular labeling of mesenchymal stem cells can be achieved via incubation with LPNs. Significantly enhanced ultrasound images of these labeled stem cells were obtained in vitro and in vivo. More importantly, the labeled stem cells could be tracked by ultrasound imaging for up to 5 days. Additional evaluation found that the in vivo detection limit achieved 2,000 labeled stem cells in the subcutaneous tissues of living mice. Our study presents a strategy to achieve real-time ultrasound imaging tracking, paving the way for an investigation on the underlying mechanism and future clinical application of stem cell therapy.