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  1. Article ; Online: Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Lung Diseases

    Soraia C. Abreu / Miquéias Lopes-Pacheco / Daniel J. Weiss / Patricia R. M. Rocco

    Frontiers in Cell and Developmental Biology, Vol

    Current Status and Perspectives

    2021  Volume 9

    Abstract: Extracellular vesicles (EVs) have emerged as a potential therapy for several diseases. These plasma membrane-derived fragments are released constitutively by virtually all cell types—including mesenchymal stromal cells (MSCs)—under stimulation or ... ...

    Abstract Extracellular vesicles (EVs) have emerged as a potential therapy for several diseases. These plasma membrane-derived fragments are released constitutively by virtually all cell types—including mesenchymal stromal cells (MSCs)—under stimulation or following cell-to-cell interaction, which leads to activation or inhibition of distinct signaling pathways. Based on their size, intracellular origin, and secretion pathway, EVs have been grouped into three main populations: exosomes, microvesicles (or microparticles), and apoptotic bodies. Several molecules can be found inside MSC-derived EVs, including proteins, lipids, mRNA, microRNAs, DNAs, as well as organelles that can be transferred to damaged recipient cells, thus contributing to the reparative process and promoting relevant anti-inflammatory/resolutive actions. Indeed, the paracrine/endocrine actions induced by MSC-derived EVs have demonstrated therapeutic potential to mitigate or even reverse tissue damage, thus raising interest in the regenerative medicine field, particularly for lung diseases. In this review, we summarize the main features of EVs and the current understanding of the mechanisms of action of MSC-derived EVs in several lung diseases, such as chronic obstructive pulmonary disease (COPD), pulmonary infections [including coronavirus disease 2019 (COVID-19)], asthma, acute respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and cystic fibrosis (CF), among others. Finally, we list a number of limitations associated with this therapeutic strategy that must be overcome in order to translate effective EV-based therapies into clinical practice.
    Keywords biomarkers ; cell therapy ; extracellular vesicles ; inflammation ; remodeling ; respiratory disease ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Impact of different frequencies of controlled breath and pressure-support levels during biphasic positive airway pressure ventilation on the lung and diaphragm in experimental mild acute respiratory distress syndrome.

    Alessandra F Thompson / Lillian Moraes / Nazareth N Rocha / Marcos V S Fernandes / Mariana A Antunes / Soraia C Abreu / Cintia L Santos / Vera L Capelozzi / Cynthia S Samary / Marcelo G de Abreu / Felipe Saddy / Paolo Pelosi / Pedro L Silva / Patricia R M Rocco

    PLoS ONE, Vol 16, Iss 8, p e

    2021  Volume 0256021

    Abstract: Background We hypothesized that a decrease in frequency of controlled breaths during biphasic positive airway pressure (BIVENT), associated with an increase in spontaneous breaths, whether pressure support (PSV)-assisted or not, would mitigate lung and ... ...

    Abstract Background We hypothesized that a decrease in frequency of controlled breaths during biphasic positive airway pressure (BIVENT), associated with an increase in spontaneous breaths, whether pressure support (PSV)-assisted or not, would mitigate lung and diaphragm damage in mild experimental acute respiratory distress syndrome (ARDS). Materials and methods Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 hours, animals were randomly assigned to: 1) BIVENT-100+PSV0%: airway pressure (Phigh) adjusted to VT = 6 mL/kg and frequency of controlled breaths (f) = 100 bpm; 2) BIVENT-50+PSV0%: Phigh adjusted to VT = 6 mL/kg and f = 50 bpm; 3) BIVENT-50+PSV50% (PSV set to half the Phigh reference value, i.e., PSV50%); or 4) BIVENT-50+PSV100% (PSV equal to Phigh reference value, i.e., PSV100%). Positive end-expiratory pressure (Plow) was equal to 5 cmH2O. Nonventilated animals were used for lung and diaphragm histology and molecular biology analysis. Results BIVENT-50+PSV0%, compared to BIVENT-100+PSV0%, reduced the diffuse alveolar damage (DAD) score, the expression of amphiregulin (marker of alveolar stretch) and muscle atrophy F-box (marker of diaphragm atrophy). In BIVENT-50 groups, the increase in PSV (BIVENT-50+PSV50% versus BIVENT-50+PSV100%) yielded better lung mechanics and less alveolar collapse, interstitial edema, cumulative DAD score, as well as gene expressions associated with lung inflammation, epithelial and endothelial cell damage in lung tissue, and muscle ring finger protein 1 (marker of muscle proteolysis) in diaphragm. Transpulmonary peak pressure (Ppeak,L) and pressure-time product per minute (PTPmin) at Phigh were associated with lung damage, while increased spontaneous breathing at Plow did not promote lung injury. Conclusion In the ARDS model used herein, during BIVENT, the level of PSV and the phase of the respiratory cycle in which the inspiratory effort occurs affected lung and diaphragm damage. Partitioning of inspiratory effort and transpulmonary pressure in ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Mesenchymal stromal cell therapy reduces lung inflammation and vascular remodeling and improves hemodynamics in experimental pulmonary arterial hypertension

    Lucas de Mendonça / Nathane S. Felix / Natália G. Blanco / Jaqueline S. Da Silva / Tatiana P. Ferreira / Soraia C. Abreu / Fernanda F. Cruz / Nazareth Rocha / Patrícia M. Silva / Vanessa Martins / Vera L. Capelozzi / Gizele Zapata-Sudo / Patricia R. M. Rocco / Pedro L. Silva

    Stem Cell Research & Therapy, Vol 8, Iss 1, Pp 1-

    2017  Volume 15

    Abstract: Abstract Background Experimental research has reported beneficial effects of mesenchymal stromal cell (MSC) therapy in pulmonary arterial hypertension (PAH). However, these studies either were based on prophylactic protocols or assessed basic remodeling ... ...

    Abstract Abstract Background Experimental research has reported beneficial effects of mesenchymal stromal cell (MSC) therapy in pulmonary arterial hypertension (PAH). However, these studies either were based on prophylactic protocols or assessed basic remodeling features without evaluating possible mechanisms. We analyzed the effects of MSC therapy on lung vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. Methods Twenty-eight Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, while a control group received saline (SAL) instead. On day 14, both groups were further randomized to receive 105 adipose-derived MSCs or SAL intravenously (n = 7/group). On day 28, right ventricular systolic pressure (RVSP) and the gene expression of mediators associated with apoptosis, inflammation, fibrosis, Smad-1 levels, cell proliferation, and endothelial–mesenchymal transition were determined. In addition, lung histology (smooth muscle cell proliferation and plexiform-like injuries), CD68+ and CD163+ macrophages, and plasma levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were evaluated. Results In the PAH group, adipose-derived MSCs, compared to SAL, reduced mean RVSP (29 ± 1 vs 39 ± 2 mmHg, p < 0.001), lung tissue collagen fiber content, smooth muscle cell proliferation, CD68+ macrophages, interleukin-6 expression, and the antiapoptotic mediators Bcl-2 and survivin. Conversely, expression of the proapoptotic mediator procaspase-3 and plasma VEGF increased, with no changes in PDGF. In the pulmonary artery, MSCs dampened the endothelial–mesenchymal transition. Conclusion In MCT-induced PAH, MSC therapy reduced lung vascular remodeling, thus improving hemodynamics. These beneficial effects were associated with increased levels of proapoptotic markers, mesenchymal-to-endothelial transition, reduced cell proliferation markers, and inflammation due to a shift away from the ...
    Keywords Pulmonary arterial hypertension ; Mesenchymal stromal cells ; Hemodynamics ; Lung vascular remodeling ; Macrophage phenotype ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
    Subject code 610
    Language English
    Publishing date 2017-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Bone Marrow Mononuclear Cell Therapy Led to Alveolar-Capillary Membrane Repair, Improving Lung Mechanics in Endotoxin-Induced Acute Lung Injury

    Luiz Felipe M. Prota / Roberta M. Lassance / Tatiana Maron-Gutierrez / Raquel C. Castiglione / Cristiane Souza Baez Garcia / Maria Cristina Ebole Santana / Jackson Souza-Menezes / Soraia C. Abreu / Vivian Samoto / Marcelo Felipe Santiago / Vera Luiza Capelozzi / Christina Maeda Takiya / Patricia R. M. Rocco / Marcelo M. Morales

    Cell Transplantation, Vol

    2010  Volume 19

    Abstract: The aim of this study was to test the hypothesis that bone marrow mononuclear cell (BMDMC) therapy led an improvement in lung mechanics and histology in endotoxin-induced lung injury. Twenty-four C57BL/6 mice were randomly divided into four groups ( n = ... ...

    Abstract The aim of this study was to test the hypothesis that bone marrow mononuclear cell (BMDMC) therapy led an improvement in lung mechanics and histology in endotoxin-induced lung injury. Twenty-four C57BL/6 mice were randomly divided into four groups ( n = 6 each). In the acute lung injur;y (ALI) group, Escherichia coli lipopolysaccharide (LPS) was instilled intratracheally (40 μg, IT), and control (C) mice received saline (0.05 ml, IT). One hour after the administration of saline or LPS, BMDMC (2 × 10 7 cells) was intravenously injected. At day 28, animals were anesthetized and lung mechanics [static elastance ( E st ), resistive (Δ P 1 ), and viscoelastic (Δ P 2 ) pressures] and histology (light and electron microscopy) were analyzed. Immunogold electron microscopy was used to evaluate if multinucleate cells were type II epithelial cells. BMDMC therapy prevented endotoxin-induced lung inflammation, alveolar collapse, and interstitial edema. In addition, BMDMC administration led to epithelial and endothelial repair with multinucleated type II pneumocytes. These histological changes yielded a reduction in lung E st , Δ P 1 , and Δ P 2 compared to ALI. In the present experimental ALI model, the administration of BMDMC yielded a reduction in the inflammatory process and a repair of epithelium and endothelium, reducing the amount of alveolar collapse, thus leading to an improvement in lung mechanics.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2010-08-01T00:00:00Z
    Publisher SAGE Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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