Triple-modal imaging of stem-cells labeled with multimodal nanoparticles, applied in a stroke model

• Published in: World journal of stem cells 2019-02, Vol.11 (2), p.100-123
• Main Authors: da Silva, Helio Rodrigues, Mamani, Javier Bustamante, Nucci, Mariana Penteado, Nucci, Leopoldo Penteado, Kondo, Andrea Tiemi, Fantacini, Daianne Maciely Carvalho, de Souza, Lucas Eduardo Botelho, Picanço-Castro, Virginia, Covas, Dimas Tadeu, Kutner, José Mauro, de Oliveira, Fernando Anselmo, Hamerschlak, Nelson, Gamarra, Lionel Fernel
• Format: Article
• Language: English
• Subjects: Basic Study
• ISSN: 1948-0210; 1948-0210
• DOI: 10.4252/wjsc.v11.i2.100

Mesenchymal stem cells (MSCs) have been widely tested for their therapeutic efficacy in the ischemic brain and have been shown to provide several benefits. A major obstacle to the clinical translation of these therapies has been the inability to noninvasively monitor the best route, cell doses, and collateral effects while ensuring the survival and effective biological functioning of the transplanted stem cells. Technological advances in multimodal imaging have allowed monitoring of the biodistribution and viability of transplanted stem cells due to a combination of imaging technologies associated with multimodal nanoparticles (MNPs) using new labels and covers to achieve low toxicity and longtime residence in cells. To evaluate the sensitivity of triple-modal imaging of stem cells labeled with MNPs and applied in a stroke model. After the isolation and immunophenotypic characterization of human bone marrow MSCs (hBM-MSCs), our team carried out lentiviral transduction of these cells for the evaluation of bioluminescent images (BLIs) and . In addition, MNPs that were previously characterized (regarding hydrodynamic size, zeta potential, and optical properties), and were used to label these cells, analyze cell viability the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and BLI analysis, and quantify the internalization process and iron load in different concentrations of MNPs magnetic resonance imaging (MRI), near-infrared fluorescence (NIRF), and inductively coupled plasma-mass spectrometry (ICP-MS). In analyses, the same labeled cells were implanted in a sham group and a stroke group at different times and under different MNP concentrations (after 4 h or 6 d of cell implantation) to evaluate the sensitivity of triple-modal images. hBM-MSC collection and isolation after immunophenotypic characterization were demonstrated to be adequate in hBM samples. After transduction of these cells with luciferase (hBM-MSC ), we detected a maximum BLI intensity of 2.0 x 10 photons/s in samples of 10 hBM-MSCs. Analysis of the physicochemical characteristics of the MNPs showed an average hydrodynamic diameter of 38.2 ± 0.5 nm, zeta potential of 29.2 ± 1.9 mV and adequate colloidal stability without agglomeration over 18 h. The signal of iron load internalization in hBM-MSC showed a close relationship with the corresponding MNP-labeling concentrations based on MRI, ICP-MS and NIRF. Under the highest MNP concentration, cellular viability showed a reduct