Cerium dioxide nanoparticles protect cardiac progenitor cells against the oxidative stress

Abstract

In the last decade, the combined applications of nano- and stem cell technology are among the newest approaches in regenerative medicine and Tissue Engineering (TE). In this context, the possibility to fabricate scaffolds with composite materials consisting of a polymer matrix and nanoparticles (NPs) as structural elements could allow to develop a novel generation of bioactive materials, capable of directing and controlling cell behavior. In particular, cerium dioxide (CeO2) NPs are promising tools to scavenge reactive oxygen species (ROS) and to confer protection to cells from the oxidative stress owing to cerium ability to switch the oxidation state (Ce4+/Ce3+). In the present experimental study, 10, 25, or 50 μg/mL CeO2 powder was administered to murine adult cardiac progenitor cells (CPCs) in complete medium for 24 hours (h) and the effects onto cells evaluated at 1, 3 and 7 days (d) from the ceria powder withdrawal from the culture. After a single 24 h CeO2 pulse, CPCs were able to take up the NPs and retain them inside the cytosol, while preserving their stemness phenotype and multipotential capability at all time-points considered. Moreover, when challenged with 50 μM H2O2 for 30 min, CeO2-treated CPCs were protected from the oxidative stress. In particular, after 24 h, only the highest concentration was protective; after 7 d, ROS levels were mitigated with all concentrations. This study demonstrated that internalized CeO2 NPs can act as a long-term defense against the oxidative insult. NPs were activated only when cells were hit by an external oxidative perturbation, remaining inert in respect to the main CPC characteristics. In conclusion, these results suggest that CeO2 nanoparticles hold an enormous potential in TE treatments protecting stem cells against the oxidative damage.