In vitro angiogenic performance and in vivo brain targeting of magnetized endothelial progenitor cells for neurorepair therapies
Elisa Carenza, Verónica Barceló, Anna Morancho, Lisa Levander, Cristina Boada, Anna Laromaine, Anna Roig*, Joan Montaner, Anna Rosell*;
Nanomedicine: Nanotechnology, Biology and Medicine
Endothelial progenitor cells (EPCs) represent a promising approach for cell-based therapies to induce tissue repair; however, their effective delivery into the brain has remained a challenge. We loaded EPCs with superparamagnetic iron oxide nanoparticles (SPIONs), assessed their angiogenic potential and evaluated their guidance to the brain using an external magnet. SPIONs were stored in the cytoplasm within endosomes/lysosomes as observed by transmission electron microscopy (TEM) and could be visualized as hypointense signals by magnetic resonance imaging (MRI) T2-weighted images. In vitro SPION-loaded EPCs were fully functional, forming vessel-like structures in Matrigel®, and displayed enhanced migration and secretion of growth factors (VEGF and FGF), which was associated with a moderate increase in reactive oxygen species production. Furthermore, in vivo MRI of treated mice showed accumulated hypointense signals consistent with SPION-loaded EPCs engraftment. Thus, we demonstrate that loading EPCs with SPIONs represents a safe and effective strategy for precise cell guidance into specific brain areas.
Endothelial Progenitor cells (EPCs) treatment might become a promising therapy to enhance neurorepair in the injured brain, but its delivery is certainly challenging. We propose that EPCs can be labeled with iron oxide superparamagnetic nanoparticles, enhance certain angiogenic abilities and guide them into specific brain areas by using an external magnetic field.