Sonoporation-based labeling of mesenchymal stem cells with polymeric MRI contrast agents for live-cell tracking

Cell transplantation has the potential to improve repair of injured tissue function; however, it is not clear how transplanted cells participate in functional recovery. We have recently succeeded in tracking millions of transplanted living cells using a polymeric MRI contrast agent, which was delivered into monolayer-cultured cells through electroporation. However, when cells were labeled using a conventional electroporation method, only cells localized around the electrode were labeled. To improve the percentage of labeled cells and to be able to start with fewer cells, we focused on a homogeneous cell labeling system. In this study, we optimized the sonoporation of a suspension culture with microbubbles for labeling and MR tracking of mesenchymal stem cells (MSCs). When water was used as the transmission medium between the acoustic probe and cell suspension, microbubbles gently collapsed with minimal cell damage. Under this condition, the number of labeled MSCs was 25%, which is 3.3-fold greater than the number of MSCs labeled using the previous system, and the cell viability was maintained at approximately 80%. The MRI signal could be clearly observed for 2.0 × 106 MSCs. These results suggest that sonoporation can efficiently introduce the polymeric contrast agent into MSCs.