Maximum Efficacy of Mesenchymal Stem Cells in Rat Model of Renal Ischemia-Reperfusion Injury: Renal Artery Administration with Optimal Numbers

Backgrounds: Despite the potential therapeutic benefits, cell therapy in renal ischemia-reperfusion (I/R) injury is currently limited by low rates of cell engraftment after systemic delivery. In this study, we investigate whether locally administration through renal artery can enhance the migration and therapeutic potential of mesenchymal stem cells (MSCs) in ischemic kidney. Methods: The model of renal I/R injury was induced by 45 min occlusion of the left renal pedicle and right nephrectomy in rat. Followed by reperfusion, graded doses of CM-Dil labeled MSCs were implanted via three routes: tail vein (TV), carotid artery (CA), and renal artery (RA). Renal blood flow was evaluated by color and spectral Doppler ultrasound at 1 h and 24 h post-I/R. All the samples were collected for analysis at 24 h post-I/R. Results: After injection of 1x10(6) MSCs, RA group showed obviously increased renal retention of grafted MSCs compared with TV and CA group; however, the renal function was even further deteriorated. When graded doses of MSCs, the maximal therapeutic efficiency was achieved with renal artery injection of 1x10(5) MSCs, which was significantly better than TV and CA group of 1x10(6) MSCs. In addition, further fluorescent microscopic and ultrasonic examination confirmed that the aggravated renal dysfunction in RA group was due to renal hypoperfusion caused by cell occlusion. Conclusion: Administration route and dosage are two critical factors determining the efficiency of cell therapy and 1x10(5) MSCs injected through renal artery produces the most dramatic improvement in renal function and morphology in rat model of renal I/R injury.