Research ArticleIn vitro angiogenic performance and in vivo brain targeting of magnetized endothelial progenitor cells for neurorepair therapies
Graphical Abstract
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.
Section snippets
Synthesis of the SPIONs in organic solvent and ligand transfer to aqueous dispersions
Synthesis of the SPIONs was adapted from a previous procedure of thermal decomposition of an iron precursor in organic media using oleic acid and oleylamine as surfactants.31 Detailed information can be found in the Supplementary Materials. The final material consisted of a stable colloidal nanoparticle dispersion at pH 7.5. A typical batch was made up of 50-nm SPION aggregates, as determined by dynamic light scattering (DLS), and − 40-mV Z-potential values.
Transmission electron microscopy (TEM)
SPIONs were examined using a JEOL1210
SPION characterization
SPIONs were synthesized through thermal decomposition reactions of iron acetylacetonate [Fe(acac)3] to yield nanoparticles, which were stabilized in hexane. SPIONs were found to display an average diameter of 6 nm and a polydispersity of 20% (Figure 1, A). Moreover, a redox titration procedure was used to determine the presence of Fe+ 3 and Fe+ 2 ions (85% and 15%, respectively), revealing a mixed composition of Fe3O4 and γ-Fe2O3. Following synthesis, the SPIONs were transferred to water using
Discussion
In the present study, we demonstrated that the magnetization of EPCs using an aqueous colloidal suspension of SPIONs is safe. In addition, we showed that magnetized OECs from stroke patients retained their ability to form tubes. Strikingly, these SPION-loaded OECs also displayed enhanced migration and secretion of growth factors, such as VEGF and FGF, which was associated with a moderate increase in ROS production. Finally, after intravenous administration of magnetized EPCs, the cells could be
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2021, Acta BiomaterialiaCitation Excerpt :SPIONs have been extensively validated for cancer therapies either as carriers of anti-cancer drugs [23] or as hyperthermic agents. [24] Although a few studies have recently yielded insight into their use as drug, gene and growth factor carriers for neuroregeneration [25,26] some studies have also shown their utility as cell labelers for field gradient-assisted cell therapies for spinal cord injury using bone marrow-derived MSC (BMMSC) [27–30] In addition, iron oxide nanoparticles internalization by SC and in vitro magnetic targeting has been recently proposed as a potential method to promote PNS regeneration, [31] although to the best of our knowledge, no in vivo studies have been reported on magnetically targeted MSC for PNS regeneration.
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Conflicts of interest: The authors have no conflicts of interest to declare.
Sources of support: A. Rosell is supported by the Miguel Servet program (CP09/00265) from the Spanish Ministry of Health (Instituto de Salud Carlos III) and A.L. by the Ramon y Cajal program 2010. This work has been funded by Instituto de Salud Carlos III: Grant PI10/00694 co-financed by the European Regional Development Fund (ERDF) and the stroke research network RENEVAS (RD06/0026/0010); the Spanish Ministry of Science and Innovation: EUROSALUD program, MAT2012-35324 and CONSOLIDER-Nanoselect-CSD2007-00041; and the European Commission FP7-People-2011-CIG 303630 project.