A positively charged small-molecule T1 magnetic resonance imaging contrast agent for highly efficient labeling and tracking adipose tissue-derived stem cells

Abstract Stem cells have great promise in regenerative medicine, and in vivo visualization of transplanted stem cells with noninvasive technique is essential for tracking and monitoring cell behaviors. Herein, a small-molecule T1 contrast agent with positive charge was prepared for efficiently labeling adipose-derived stem cells (ADSCs) in vitro and in vivo. The contrast agent was synthesized by conjugating quaternary ammonium salt onto DO3A (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7-triacetic acid) skeleton via nucleophilic reaction, then chelating gadolinium ion to form Gd-HP-DO3A-TA complex. The Gd-HP-DO3A-TA exhibited a similar longitudinal relaxivity (4.42 mM−1 s−1) as commercial contrast agent (Gd-DTPA), but it can be efficiently internalized by ADSCs, leading to remarkably enhanced cellular magnetic resonance imaging (MRI) signal intensity without negative effects on viability, proliferation and multi-differentiation potential of ADSCs. Moreover, in vivo experiments revealed that Gd-HP-DO3A-TA-labeled ADSCs can home to the injured liver region with enhanced signal contrast and promote to rebuild liver function. Our results indicate that the small-molecule T1 contrast agent with positive charge has great potential for stem cells labeling and MRI tracking.