Abstract
BACKGROUND: Acute kidney injury (AKI) is characterized by the abrupt loss of renal function and lack of curative therapies. Placental-derived mesenchymal stem cells (PL-MSCs) have shown promise in regenerative medicine, including in the treatment of AKI. However, optimizing the therapeutic effects of PL-MSCs remains a critical objective. Magnetic targeting is one potential avenue of optimization. Using iron oxide-labeled MSCs with an external magnetic field to increase cell homing ability may be an ideal method for improving the cell therapy effects in vivo. METHODS: In this study, PL-MSCs were labeled with Fe(3)O(4) nanoparticles coated with polydopamine (Fe(3)O(4)@PDA NPs) for 24 h, and cell efficiency and viability were tested. The conditionally immortalized mice renal tubular endothelial cells (mRTECs) were incubated with cisplatin (Cis) and co-cultured with non-labeled or NP-labeled MSCs. The protective effect of NP-labeled MSCs on mRTEC was evaluated. In in vivo experiments, non-labeled or NP-labeled MSCs, with or without an external magnetic field, were injected into mice with Cis-induced AKI. The blood and tissue samples were collected to assess renal function and tissue damage. RESULTS: The study confirmed that MSCs or MSC-NP can significantly improve Cis-induced mRTEC injury. In addition, NP-labeled MSCs with an external magnetic field (magnetically-targeted MSCs) improved their homing to the kidney tissues in mice with AKI, resulting in enhanced kidney function compared with those of mice treated with MSC or NP-labeled MSC treatment alone. Moreover, magnetically-targeted MSCs alleviated renal injury through suppressing oxidative stress and inflammation, reducing cell apoptosis, and promoting cell proliferation. CONCLUSION: Magnetic targeting enhances the therapeutic effects of PL-MSCs on Cis-induced AKI in mice, suggesting that magnetically-targeted MSCs could serve as potential treatments for patients with Cis-induced AKI.