Superparamagnetic Iron Oxide-Loaded Cationic Polymersomes for Cellular MR Imaging of Therapeutic Stem Cells in Stroke

MR imaging (MRI) upon cell labeling is an attractive and clinically translatable tool for longitudinally monitoring the survival and migration of stem cells. The common intracellular delivery of superparamagnetic iron oxide nanoparticles (SPIONs) via poly-L-lysine (PLL) requires a high SPION concentration and a long incubation period for appropriate cell labeling, which may negatively affect the viability and function of stem cells. In this study, we determined the performance of a new class of cationic polymersomes in transferring SPIONs into green fluorescence protein-modified mesenchymal stem cells (MSCs) for cellular MRI in acute ischemic stroke, compared with PLL-coated SPIONs. The results demonstrated that the polymersomes had comparable labeling efficiency and biological safety as well as a marginal benefit on post-transplantation cell survival; the polymersomes had the advantages of a relatively low SPION concentration and a substantially shorter labeling period compared with PLL-coated SPIONs. After transplantation, MSCs labeled using both methods offered a similar therapeutic effect on stroke, and cellular MRI could track the in vivo distribution and migration behavior of biologically active MSCs; however, MRI overestimated the true size of the cell grafts. SPION-loaded cationic polymersomes can be used as an alternative for the efficient, rapid, and safe labeling of stem cells for cellular MRI.