Stem cell homing, tracking and therapeutic efficiency evaluation for stroke treatment using nanoparticles: A systematic review

Nucci, Mariana Penteado; Filgueiras, Igor Salerno; Ferreira, João José Pinto; Oliveira, Fernando A.; Nucci, Leopoldo Penteado; Mamani, Javier Bustamante; Rego, Gabriel N. A.; Gamarra, Lionel Fernel

doi:10.4252/wjsc.v12.i5.381

Cited by 15 publications

(17 citation statements)

References 71 publications

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“…Generally, studies about cell homing/tracking after ischemia injury have used ex vivo techniques to quantify MSC in recipient animals; however, this form of analysis cannot yield longitudinal data about the migration or graft dynamic in a single animal. Noninvasive molecular imaging techniques, such as magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), near-infrared fluorescence (NIRF) imaging, and bioluminescence imaging (BLI) could be used to home and track these cells in vivo by labeling cells with a contrast agent [13].…”

Section: Introductionmentioning

confidence: 99%

“…In preclinical studies, cell labeling with superparamagnetic iron oxide nanoparticles (SPION) has been widely used as a tracking method, and its combination with nearinfrared (NIR) dye, known as a bimodal technique, demonstrated a greater ability of penetration and revealed deeper tissues [14]. With the use of innovative NIRF probes and optical instruments, in vivo fluorescence imaging has grown significantly, allowing for the evaluation of dynamic migration and distribution of transplanted MSC as well as tissue regeneration based on stem cells [13]. Bimodal analysis may necessitate genetic cell modification to express luciferase enzyme signal [15], allowing BLI technique to be used as a supplement to NIRF imaging, therefore improving ischemic and inflammatory monitoring, as well as tracking viable cells after engraftment reduction [13].…”

Section: Introductionmentioning

confidence: 99%

“…With the use of innovative NIRF probes and optical instruments, in vivo fluorescence imaging has grown significantly, allowing for the evaluation of dynamic migration and distribution of transplanted MSC as well as tissue regeneration based on stem cells [13]. Bimodal analysis may necessitate genetic cell modification to express luciferase enzyme signal [15], allowing BLI technique to be used as a supplement to NIRF imaging, therefore improving ischemic and inflammatory monitoring, as well as tracking viable cells after engraftment reduction [13].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysis

Nucci

Oliveira

Ferreira

et al. 2022

Cells

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The goal of this study is to see how combining physical activity with cell treatment impacts functional recovery in a stroke model. Molecular imaging and multimodal nanoparticles assisted in cell tracking and longitudinal monitoring (MNP). The viability of mesenchymal stem cell (MSC) was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and bioluminescent image (BLI) after lentiviral transduction and MNP labeling. At random, the animals were divided into 5 groups (control-G1, and experimental G2-G5). The photothrombotic stroke induction was confirmed by local blood perfusion reduction and Triphenyltetrazolium chloride (TTC), and MSC in the G3 and G5 groups were implanted after 24 h, with BLI and near-infrared fluorescence image (NIRF) tracking these cells at 28 h, 2, 7, 14, and 28 days. During a 28-day period, the G5 also conducted physical training, whereas the G4 simply did the training. At 0, 7, 14, and 28 days, the animals were functionally tested using a cylinder test and a spontaneous motor activity test. MNP internalization in MSC was confirmed using brightfield and fluorescence microscopy. In relation to G1 group, only 3% of cell viability reduced. The G2–G5 groups showed more than 69% of blood perfusion reduction. The G5 group performed better over time, with a progressive recovery of symmetry and an increase of fast vertical movements. Up to 7 days, BLI and NIRF followed MSC at the damaged site, demonstrating a signal rise that could be connected to cell proliferation at the injury site during the acute phase of stroke. Local MSC therapy mixed with physical activity resulted in better results in alleviating motor dysfunction, particularly during the acute period. When it comes to neurorehabilitation, this alternative therapy could be a suitable fit.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysis

Nucci

Oliveira

Ferreira

et al. 2022

Cells

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“…Accordingly, some researchers have used MRI [ 89 , 119 , 126 ] or positron emission tomography–CT [ 127 , 128 ] to evaluate infarct volume in live animals. Nanoparticle technology is able to detect and chase transplanted stem cells using MRI in live animals [ 119 , 129 , 130 ].…”

Section: Imaging Techniques For Stem Cell Therapymentioning

confidence: 99%

Prospects of Therapeutic Target and Directions for Ischemic Stroke

Kim¹,

Kim

Lee

et al. 2021

Pharmaceuticals

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Stroke is a serious, adverse neurological event and the third leading cause of death and disability worldwide. Most strokes are caused by a block in cerebral blood flow, resulting in neurological deficits through the death of brain tissue. Recombinant tissue plasminogen activator (rt-PA) is currently the only immediate treatment medication for stroke. The goal of rt-PA administration is to reduce the thrombus and/or embolism via thrombolysis; however, the administration of rt-PA must occur within a very short therapeutic timeframe (3 h to 6 h) after symptom onset. Components of the pathological mechanisms involved in ischemic stroke can be used as potential biomarkers in current treatment. However, none are currently under investigation in clinical trials; thus, further studies investigating biomarkers are needed. After ischemic stroke, microglial cells can be activated and release inflammatory cytokines. These cytokines lead to severe neurotoxicity via the overactivation of microglia in prolonged and lasting insults such as stroke. Thus, the balanced regulation of microglial activation may be necessary for therapy. Stem cell therapy is a promising clinical treatment strategy for ischemic stroke. Stem cells can increase the functional recovery of damaged tissue after post-ischemic stroke through various mechanisms including the secretion of neurotrophic factors, immunomodulation, the stimulation of endogenous neurogenesis, and neovascularization. To investigate the use of stem cell therapy for neurological diseases in preclinical studies, however, it is important to develop imaging technologies that are able to evaluate disease progression and to “chase” (i.e., track or monitor) transplanted stem cells in recipients. Imaging technology development is rapidly advancing, and more sensitive techniques, such as the invasive and non-invasive multimodal techniques, are under development. Here, we summarize the potential risk factors and biomarker treatment strategies, stem cell-based therapy and emerging multimodal imaging techniques in the context of stroke. This current review provides a conceptual framework for considering the therapeutic targets and directions for the treatment of brain dysfunctions, with a particular focus on ischemic stroke.

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“…We can also highlight techniques such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT) and Fluorescence Imaging (FLI), and especially Near-infrared fluorescence (NIRF) that enables the capture of images with greater depth of penetration than fluorescent agents in the visible spectrum, reducing the autofluorescence of tissues [19]. Each of these image modalities has advantages and limitations when compared to any other, which is why the development of probes which make it possible to perform a set of images with a single tracking agent has gained a lot of attention due to the multimodal images generated [17,20]. The last systematic review on this topic, Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model, did not show the combined use of the molecular image technique in any of the studies analyzed [17].…”

Section: Introductionmentioning

confidence: 99%

Multimodal Tracking of Hematopoietic Stem Cells from Young and Old Mice Labeled with Magnetic–Fluorescent Nanoparticles and Their Grafting by Bioluminescence in a Bone Marrow Transplant Model

et al. 2021

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This study proposes an innovative way to evaluate the homing and tracking of hematopoietic stem cells from young and old mice labeled with SPIONNIRF-Rh conjugated with two types of fluorophores (NIRF and Rhodamine), and their grafting by bioluminescence (BLI) in a bone marrow transplant (BMT) model. In an in vitro study, we isolated bone marrow mononuclear cells (BM-MNC) from young and old mice, and analyzed the physical–chemical characteristics of SPIONNIRF-Rh, their internalization, cell viability, and the iron quantification by NIRF, ICP-MS, and MRI. The in vivo study was performed in a BMT model to evaluate the homing, tracking, and grafting of young and old BM-MNC labeled with SPIONNIRF-Rh by NIRF and BLI, as well as the hematological reconstitution for 120 days. 5FU influenced the number of cells isolated mainly in young cells. SPIONNIRF-Rh had adequate characteristics for efficient internalization into BM-MNC. The iron load quantification by NIRF, ICP-MS, and MRI was in the order of 104 SPIONNIRF-Rh/BM-MNC. In the in vivo study, the acute NIRF evaluation showed higher signal intensity in the spinal cord and abdominal region, and the BLI evaluation allowed follow-up (11–120 days), achieving a peak of intensity at 30 days, which remained stable around 108 photons/s until the end. The hematologic evaluation showed similar behavior until 30 days and the histological results confirm that iron is present in almost all tissue evaluated. Our results on BM-MNC homing and tracking in the BMT model did not show a difference in migration or grafting of cells from young or old mice, with the hemogram analysis trending to differentiation towards the myeloid lineage in mice that received cells from old animals. The cell homing by NIRF and long term cell follow-up by BLI highlighted the relevance of the multimodal nanoparticles and combined techniques for evaluation.

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Stem cell homing, tracking and therapeutic efficiency evaluation for stroke treatment using nanoparticles: A systematic review

Cited by 15 publications

References 71 publications

Effect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysis

Effect of Cell Therapy and Exercise Training in a Stroke Model, Considering the Cell Track by Molecular Image and Behavioral Analysis

Prospects of Therapeutic Target and Directions for Ischemic Stroke

Multimodal Tracking of Hematopoietic Stem Cells from Young and Old Mice Labeled with Magnetic–Fluorescent Nanoparticles and Their Grafting by Bioluminescence in a Bone Marrow Transplant Model

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