Supermagnetic nanoparticles for cell tracking and magnetic vectorization n ischemic stroke = Nanopartículas superparamagnéticas para seguimiento celular y vectorización magnética en el ictus isquémico

Resumo

Cerebrovascular diseases are the second cause of death and the first cause of disability in developed countries. However, therapies for these diseases are quite limited. So far, pharmacological thrombolysis or mechanical reperfusion are the strategies that report higher benefits in the acute phase for the patients, in terms of neurological outcome, being the recombinant tissue plasminogen activator (rt-PA) the most common thrombolytic agent. Cell based therapies have emerged as a promissing approaches to conventional pharmacological treatments due to their multipotential action mechanisms. Integration in the host, immunomodulation processes or growth factors secretion are the possible ways of action, however fundamental questions related to cell type, characterization and dosage, therapeutic timing versus toxicity or the relationship between biodistribution, fate and outcome must be elucidated. A large number of preclinical and clinical trials have used systemic infusion of these cells, nevertheless it is still necessary to understand if transplanted MSCs can home to and engraft at ischemic and injured sites in the brain to exert their therapeutic effects. Several imaging techniques combined with cellular labeling agents have been developed to monitor the fate of injected cells following different administration routes. However, for stem cell therapy the goal of imaging techniques is double. On one hand is crucial to determine where and when the cells are, but on the other hand imaging modality is also important to evaluate the pathological progress of the target organ as well. Nowadays, magnetic resonance imaging (MRI) is one of the most powerful medical diagnostic tools available due to the high resolution images, but also because of the non-invasive and no ionizing radiation nature of the technique. Nevertheless, administered cells are too small to be detectable in MRI. The use of biocompatible contrast agents can overcome this limitation. Thus, superparamagnetic nanoparticles are an excellent tool for stem cell labeling, not only for the high quality of the MRI image, for the low toxicity and the ease for tagging as well. Overall, in this work we have hypothesized that it is possible to synthesize biocompatible superparamagnetic nanoparticles for in vivo cell tracking. Superparamagnetic nanoparticles-tagged cells can be monitored in vivo by MRI and guided with magnetic fields without harmful effects, providing information of the cellular fate after different routes of administration. Moreover, the nanoparticle labeling will allow us to study therapeutic effects in an animal model of ischemic stroke based on the localization of the cells after delivery.