Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations

International Journal of Nanomedicine Dovepress open access to scientific and medical research Review Open Access Full Text Article International Journal of Nanomedicine downloaded from https://www.dovepress.com/ For personal use only. Tracking stem cells with superparamagnetic iron oxide nanoparticles: perspectives and considerations This article was published in the following Dove Press journal: International Journal of Nanomedicine 25 January 2017 Number of times this article has been viewed Jasmin 1,* Gustavo Torres de Souza 2,3,* Ruy Andrade Louzada 4 Paulo Henrique Rosado-deCastro 5 Rosalia Mendez-Otero 6 Antonio Carlos Campos de Carvalho 6 NUMPEX-Bio, Federal University of Rio de Janeiro, Duque de Caxias, RJ, 2 Laboratory of Animal Reproduction, Embrapa Dairy Cattle, Juiz de Fora, MG, 3Laboratory of Genetics, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil; 4Institute GustaveRoussy of Oncology, Paris-Sud University, Villejuif, France; 5Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 6 Institute Carlos Chagas Filho of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil 1 *These authors contributed equally to this work Correspondence: Jasmin Estrada de Xerém, 27, NUMPEXBio – UFRJ, Xerém, Duque de Caxias, RJ, 25245-390, Brazil Tel +55 21 2679 1018 Email Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) have been used for diagnoses in biomedical applications, due to their unique properties and their apparent safety for humans. In general, SPIONs do not seem to produce cell damage, although their long-term in vivo effects continue to be investigated. The possibility of efficiently labeling cells with these magnetic nanoparticles has stimulated their use to noninvasively track cells by magnetic resonance imaging after transplantation. SPIONs are attracting increasing attention and are one of the preferred methods for cell labeling and tracking in preclinical and clinical studies. For clinical protocol approval of magnetic-labeled cell tracking, it is essential to expand our knowledge of the time course of SPIONs after cell incorporation and transplantation. This review focuses on the recent advances in tracking SPION-labeled stem cells, analyzing the possibilities and limitations of their use, not only focusing on myocardial infarction but also discussing other models. Keywords: nanoparticles, superparamagnetic iron oxide nanoparticles, stem cells, cell tracking, in vivo imaging, myocardial infarction Introduction Stem cells have emerged as a novel therapeutic option for cell death-related diseases, such as myocardial infarction. The effects of adult stem cells on damaged tissues are currently attributed mainly to proliferation, inhibition of apoptosis and inflammation, and increase in angiogenesis caused by the secretion of paracrine factors by injected stem cells, thus stimulating tissue regeneration and repair.1–4 However, the difficulty of evaluating and determining the precise contribution of each mechanism involved in cell-based treatments is one of the obstacles to their approval for clinical use.5,6 Methods to determine the biodistribution and fate of injected cells are required to understand and refine stem cell therapies in patients. The outcomes of clinical trials using stem cells are less assessable by invasive methods, which are usually used in experiments with animal models and include postmortem analyses, such as histologic analysis of tissues and organs.7,8 Currently, there are active efforts to develop and standardize suitable noninvasive methods for long-term tracking of cells after transplantation.9 Magnetic resonance imaging (MRI) offers an imaging modality that allows highresolution visualization of cell biodistribution.10–14 Several types of contrast agents have been used for MRI in vivo imaging, including superparamagnetic iron oxide nanoparticles (SPIONs), which successfully label different mammalian cell types.15–19 779 submit your manuscript | www.dovepress.com International Journal of Nanomedicine 2017:12 779–793 Dovepress © 2017 Jasmin et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/IJN.S126530 Dovepress Jasmin et al In this review, we discuss the main characteristics and limitations of molecular imaging technologies to investigate cellular biodistribution and fate. The primary focus was on SPION labeling methods for stem cells tracking in a myocardial infarction model, but we also discussed other models, markers, and molecular imaging techniques. We have reviewed the literature in the field and also provided unpublished data on mesenchymal stem cells labeling and tracking in the myocardial infarction model. For this review, we consulted relevant articles published on prominent journals for each specific area covered in the topics, provided that they were indexed on PubMed, Wiley’s Library, Science Central, and/or Google Scholar. We used the following keywords for our search: SPIONs, nanoparticles for cell labeling, cell tracking, tracking cells in myocardial infarction, in vivo cellular imaging, MRI, molecular imaging technologies, and nanoparticles toxicity. Labeling stem cells and molecular imaging methods Two main approaches are used to label cells for in vivo tracking: direct and indirect labeling. Direct labeling involves a relatively simple step of in vitro incorporation of the marker molecule before the cell therapy.20 A range of molecules can be used, and this technology is considered fairly well established and yields consistent and reproducible results. SPIONs, fluorescent dyes, or radionuclides can be used as probes to directly prelabel stem cells for noninvasive tracking.9,21–23 Standardized protocols used for labeling stem cells with SPIONs were previously compiled by us,15,24 and other direct-labeling reagents were reviewed by Marks and Nolan25 and Progatzky et al.26 Indirect labeling is a considerably different method, which includes genetic modification in order to either produce an appropriate signal-generating molecule or increase the affinity of cells to contrast agents.9,21,27–32 Transient expression of reporter proteins by DNA vector transfection is often included in this set of cell labeling.9 Another alternative is stable expression of the reporter protein by transduction of the cells with a virus. Diff (...truncated)