Stem cells labeled with superparamagnetic iron oxide nanoparticles in a preclinical model of cerebral ischemia: a systematic review with meta-analysis

Introduction: Although there is an increase in clinical trials assessing the efficacy of cell therapy in structural and functional regeneration after stroke, there are not enough data in the literature describing the best cell type to be used, the best route, and also the best nanoparticle to analyze these stem cells in vivo. This review analyzed published data on superparamagnetic iron oxide nanoparticle (SPION)-labeled stem cells used for ischemic stroke therapy.Method: We performed a systematic review and meta-analysis of data from experiments testing the efficacy of cellular treatment with SPION versus no treatment to improve behavioral or modified neural scale outcomes in animal models of stroke by the Cochrane Collaboration and indexed in EMBASE, PubMed, and Web of Science since 2000. To test the impact of study quality and design characteristics, we used random-effects meta-regression. in addition, trim and fill were used to assess publication bias.Results: the search retrieved 258 articles. After application of the inclusion criteria, 24 reports published between January 2000 and October 2014 were selected. These 24 articles were analyzed for nanoparticle characteristics, stem cell types, and efficacy in animal models.Conclusion: This study highlights the therapeutic role of stem cells in stroke and emphasizes nanotechnology as an important tool for monitoring stem cell migration to the affected neurological locus.Instituto Israelita de Ensino e Pesquisa Albert EinsteinCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPEGHosp Israelita Albert Einstein, BR-05651901 São Paulo, BrazilUniversidade Federal de São Paulo, BR-04021001 São Paulo, SP, BrazilSanta Casa Misericordia São Paulo, BR-01221020 São Paulo, SP, BrazilUniv São Paulo, Inst Matemat & Estat, BR-05508090 São Paulo, SP, BrazilUniv São Paulo, LIM44, BR-05403000 São Paulo, SP, BrazilUniversidade Federal de São Paulo, BR-04021001 São Paulo, SP, BrazilWeb of Scienc

Stem cells labeled with superparamagnetic iron oxide nanoparticles in a preclinical model of cerebral ischemia: a systematic review with meta-analysis

Abstract\ud \ud Introduction\ud Although there is an increase in clinical trials assessing the efficacy of cell therapy in structural and functional regeneration after stroke, there are not enough data in the literature describing the best cell type to be used, the best route, and also the best nanoparticle to analyze these stem cells in vivo. This review analyzed published data on superparamagnetic iron oxide nanoparticle (SPION)-labeled stem cells used for ischemic stroke therapy.\ud \ud \ud Method\ud We performed a systematic review and meta-analysis of data from experiments testing the efficacy of cellular treatment with SPION versus no treatment to improve behavioral or modified neural scale outcomes in animal models of stroke by the Cochrane Collaboration and indexed in EMBASE, PubMed, and Web of Science since 2000. To test the impact of study quality and design characteristics, we used random-effects meta-regression. In addition, trim and fill were used to assess publication bias.\ud \ud \ud Results\ud The search retrieved 258 articles. After application of the inclusion criteria, 24 reports published between January 2000 and October 2014 were selected. These 24 articles were analyzed for nanoparticle characteristics, stem cell types, and efficacy in animal models.\ud \ud \ud Conclusion\ud This study highlights the therapeutic role of stem cells in stroke and emphasizes nanotechnology as an important tool for monitoring stem cell migration to the affected neurological locus.Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE)FINEPCAPESFAPESPFAPE

Evaluation of temperature induction in focal ischemic thermocoagulation model.

The thermocoagulation model, which consists of focal cerebral ischemia with craniectomy, is helpful in studying permanent ischemic brain lesions and has good reproducibility and low mortality. This study analyzed the best conditions for inducing a focal ischemic lesion by thermocoagulation. We investigated parameters such as temperature and thermal dissipation in the brain tissue during induction and analyzed real-time blood perfusion, histological changes, magnetic resonance imaging (MRI), and motor behavior in a permanent ischemic stroke model. We used three-month-old male Wistar rats, weighing 300-350 g. In the first experiment, the animals were divided into four groups (n = 5 each): one sham surgery group and three ischemic lesion groups having thermocoagulation induction (TCI) temperatures of 200°C, 300°C, and 400°C, respectively, with blood perfusion (basal and 30 min after TCI) and 2,3,5-Triphenyl-tetrazolium chloride (TTC) evaluation at 2 h after TCI. In the second experiment, five groups (n = 5 each) were analyzed by MRI (basal and 24 h after TCI) and behavioral tests (basal and seven days after TCI) with the control group added for the surgical effects. The MRI and TTC analyses revealed that ischemic brain lesions expressively evolved, especially at TCI temperatures of 300°C and 400°C, and significant motor deficits were observed as the animals showed a decrease frequency of movement and an asymmetric pattern. We conclude that a TCI temperature of 400°C causes permanent ischemic stroke and motor deficit

Current Clinical Trials Protocols and the Global Effort for Immunization against SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is the biggest health challenge of the 21st century, affecting millions of people globally. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ignited an unprecedented effort from the scientific community in the development of new vaccines on different platforms due to the absence of a broad and effective treatment for COVID-19 or prevention strategy for SARS-CoV-2 dissemination. Based on 50 current studies selected from the main clinical trial databases, this systematic review summarizes the global race for vaccine development against COVID-19. For each study, the main intervention characteristics, the design used, and the local or global center partnerships created are highlighted. Most vaccine developments have taken place in Asia, using a viral vector method. Two purified inactivated SARS-CoV-2 vaccine candidates, an mRNA-based vaccine mRNA1273, and the chimpanzee adenoviral vaccine ChAdOx1 are currently in phase III clinical trials in the respective countries Brazil, the United Arab Emirates, the USA, and the United Kingdom. These vaccines are being developed based on a quickly formed network of collaboration

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

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

Motor behavior assessment using Actimeter and cylinder tests at basal and after 7 days of thermocoagulation induction (Experiment 2).

<p>In Actimeter test (A-F), A: Slow movement (horizontal activity), B: Fast movement (horizontal activity), C: Slow stereotyped, D: Fast stereotyped, E: Slow rearing movement (vertical activity), and F: Fast rearing movement (vertical activity). The cylinder test (G-H), G: Bilateral forelimb analyses-on the left, an animal with bilateral symmetry and on the right, an animal with asymmetry contralateral with the ischemic lesion, H: Symmetry score at basal time and seven days after induction. Both tests were performed in the five experimental groups (n = 5 per group): control, sham, ischemic with 200°C, ischemic with 300°C, and ischemic with 400°C, which were represented by the boxes that show the values of the 25th and 75th percentiles, the lines across the boxes represent the medians, and the whiskers extend to the highest and lowest values, using different shades of gray for each group. *: p<0.001 in comparison with base time, #: p<0.001 in comparison with control group, and §: p<0.001 in comparison with the sham group.</p

Estimated mean and 95% confidence interval of each group for spontaneous motor activity analysis.

<p>Estimated mean and 95% confidence interval of each group for spontaneous motor activity analysis.</p

Effect time and group for symmetric score by cylinder test.

<p>Effect time and group for symmetric score by cylinder test.</p

Ischemic lesion induction by thermocoagulation (Experiments 1 and 2).

<p>A-I: A hot probe with digital control of temperature, A-II: Fiber optic thermometer systems, B–D: Thermocoagulation induction (TCI) at 200°C, 300°C, and 400°C (red arrow) and thermal dissipation analysis in the brain tissue by using fiber optic at each temperature condition (yellow arrow) (<i>n</i> = 5 per group), E–G: Thermal dissipation analysis on the tissue brain through infrared camera at each temperature of induction, H: color of brain tissue before TCI (light red), and I: color brain tissue after TCI (dark red).</p

Estimated mean for symmetric score by cylinder test.

<p>Estimated mean for symmetric score by cylinder test.</p