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  1. Article: Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Lung Diseases: Current Status and Perspectives.

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

    Frontiers in cell and developmental biology

    2021  Volume 9, Page(s) 600711

    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.
    Language English
    Publishing date 2021-02-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2021.600711
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. 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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  3. Article ; Online: Association between breast feeding and food consumption according to the degree of processing in Brazil: a cohort study.

    Abreu de Carvalho, Carolina / Viola, Poliana Cristina de Almeida Fonseca / Magalhães, Elma Izze da Silva / Machado, Soraia Pinheiro / Matijasevich, Alicia / Menezes, Ana Maria Baptista / Tovo-Rodrigues, Luciana / Santos, Ina S / Goncalves, Helen / Wehrmeister, Fernando C / Horta, Bernardo Lessa / Moura da Silva, Antônio Augusto

    BMJ open

    2024  Volume 14, Issue 4, Page(s) e083871

    Abstract: Background: The benefits of breast feeding may be associated with better formation of eating habits beyond childhood. This study was designed to verify the association between breast feeding and food consumption according to the degree of processing in ... ...

    Abstract Background: The benefits of breast feeding may be associated with better formation of eating habits beyond childhood. This study was designed to verify the association between breast feeding and food consumption according to the degree of processing in four Brazilian birth cohorts.
    Methods: The duration of exclusive, predominant and total breast feeding was evaluated. The analysis of the energy contribution of fresh or minimally processed foods (FMPF) and ultra-processed foods (UPF) in the diet was evaluated during childhood (13-36 months), adolescence (11-18 years) and adulthood (22, 23 and 30 years).
    Results: Those who were predominantly breastfed for less than 4 months had a higher UPF consumption (β 3.14, 95% CI 0.82 to 5.47) and a lower FMPF consumption (β -3.47, 95% CI -5.91 to -1.02) at age 22 years in the 1993 cohort. Exclusive breast feeding (EBF) for less than 6 months was associated with increased UPF consumption (β 1.75, 95% CI 0.25 to 3.24) and reduced FMPF consumption (β -1.49, 95% CI -2.93 to -0.04) at age 11 years in the 2004 cohort. In this same cohort, total breast feeding for less than 12 months was associated with increased UPF consumption (β 1.12, 95% CI 0.24 to 2.19) and decreased FMPF consumption (β -1.13, 95% CI -2 .07 to -0.19). Children who did not receive EBF for 6 months showed an increase in the energy contribution of UPF (β 2.36, 95% CI 0.53 to 4.18) and a decrease in FMPF (β -2.33, 95% CI -4 .19 to -0.48) in the diet at 13-36 months in the 2010 cohort. In this cohort, children who were breastfed for less than 12 months in total had higher UPF consumption (β 2.16, 95% CI 0.81 to 3.51) and lower FMPF consumption (β -1.79, 95% CI -3.09 to -0.48).
    Conclusion: Exposure to breast feeding is associated with lower UPF consumption and higher FMPF consumption in childhood, adolescence and adulthood.
    MeSH term(s) Child ; Female ; Adolescent ; Humans ; Young Adult ; Adult ; Breast Feeding ; Cohort Studies ; Brazil ; Fast Foods ; Diet ; Food Handling
    Language English
    Publishing date 2024-04-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2024-083871
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Extracellular vesicles derived from mesenchymal stromal cells: a therapeutic option in respiratory diseases?

    Abreu, Soraia C / Weiss, Daniel J / Rocco, Patricia R M

    Stem cell research & therapy

    2016  Volume 7, Issue 1, Page(s) 53

    Abstract: Extracellular vesicles (EVs) are plasma membrane-bound fragments released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. EVs derived from MSCs and other cell types transfer molecules (such as DNA, ...

    Abstract Extracellular vesicles (EVs) are plasma membrane-bound fragments released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. EVs derived from MSCs and other cell types transfer molecules (such as DNA, proteins/peptides, mRNA, microRNA, and lipids) and/or organelles with reparative and anti-inflammatory properties to recipient cells. The paracrine anti-inflammatory effects promoted by MSC-derived EVs have attracted significant interest in the regenerative medicine field, including for potential use in lung injuries. In the present review, we describe the characteristics, biological activities, and mechanisms of action of MSC-derived EVs. We also review the therapeutic potential of EVs as reported in relevant preclinical models of acute and chronic respiratory diseases, such as pneumonia, acute respiratory distress syndrome, asthma, and pulmonary arterial hypertension. Finally, we discuss possible approaches for potentiating the therapeutic effects of MSC-derived EVs so as to enable use of this therapy in clinical practice.
    MeSH term(s) Asthma/metabolism ; Asthma/physiopathology ; Asthma/therapy ; DNA/therapeutic use ; Endocytosis ; Extracellular Vesicles/chemistry ; Extracellular Vesicles/transplantation ; Humans ; Hypertension, Pulmonary/metabolism ; Hypertension, Pulmonary/physiopathology ; Hypertension, Pulmonary/therapy ; Lipids/therapeutic use ; Lung Injury/metabolism ; Lung Injury/physiopathology ; Lung Injury/therapy ; Mesenchymal Stromal Cells/chemistry ; Mesenchymal Stromal Cells/metabolism ; MicroRNAs/therapeutic use ; Molecular Targeted Therapy ; Pneumonia, Bacterial/metabolism ; Pneumonia, Bacterial/physiopathology ; Pneumonia, Bacterial/therapy ; Proteins/therapeutic use ; RNA, Messenger/therapeutic use ; Respiratory Distress Syndrome, Adult/metabolism ; Respiratory Distress Syndrome, Adult/physiopathology ; Respiratory Distress Syndrome, Adult/therapy
    Chemical Substances Lipids ; MicroRNAs ; Proteins ; RNA, Messenger ; DNA (9007-49-2)
    Language English
    Publishing date 2016-04-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2548671-8
    ISSN 1757-6512 ; 1757-6512
    ISSN (online) 1757-6512
    ISSN 1757-6512
    DOI 10.1186/s13287-016-0317-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Iso-Oncotic Albumin Mitigates Brain and Kidney Injury in Experimental Focal Ischemic Stroke.

    Mendes, Renata de S / Martins, Gloria / Oliveira, Milena V / Rocha, Nazareth N / Cruz, Fernanda F / Antunes, Mariana A / Abreu, Soraia C / Silva, Adriana L / Takiya, Christina / Pimentel-Coelho, Pedro M / Robba, Chiara / Mendez-Otero, Rosália / Pelosi, Paolo / Rocco, Patricia R M / Silva, Pedro L

    Frontiers in neurology

    2020  Volume 11, Page(s) 1001

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2020-09-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2020.01001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Multiomics Profiling of Toxins in the Venom of the Amazonian Spider

    Nishiduka, Erika S / Abreu, Thiago F / Abukawa, Fernanda Midori / Oliveira, Ursula C / Tardivo, Caio E O / Nascimento, Soraia M / Meissner, Gabriel O / Chaim, Olga M / Juliano, Maria A / Kitano, Eduardo S / Zelanis, André / Serrano, Solange M T / da Silva, Pedro I / Junqueira-de-Azevedo, Inácio L / Nishiyama-Jr, Milton Y / Tashima, Alexandre K

    Journal of proteome research

    2022  Volume 21, Issue 11, Page(s) 2783–2797

    Abstract: Acanthoscurria ... ...

    Abstract Acanthoscurria juruenicola
    MeSH term(s) Animals ; Male ; Female ; Spiders/genetics ; Spiders/metabolism ; Spider Venoms/genetics ; Spider Venoms/chemistry ; Spider Venoms/metabolism ; Cysteine/metabolism ; Proteomics/methods ; Mass Spectrometry/methods ; Proteome/genetics ; Proteome/metabolism ; Peptides/analysis
    Chemical Substances Spider Venoms ; Cysteine (K848JZ4886) ; Proteome ; Peptides
    Language English
    Publishing date 2022-10-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.2c00593
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. 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.

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

    PloS one

    2021  Volume 16, Issue 8, Page(s) e0256021

    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 spontaneous breaths at Plow and Phigh is required to minimize VILI.
    MeSH term(s) Acute Lung Injury/pathology ; Animals ; Continuous Positive Airway Pressure/methods ; Diaphragm/pathology ; Endothelium/pathology ; Lung/pathology ; Male ; Rats ; Rats, Wistar ; Respiration ; Respiratory Distress Syndrome/physiopathology ; Respiratory Distress Syndrome/therapy ; Tidal Volume/physiology
    Language English
    Publishing date 2021-08-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0256021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. 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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  9. Article ; Online: Encapsulation of camu-camu extracts using prebiotic biopolymers: Controlled release of bioactive compounds and effect on their physicochemical and thermal properties.

    de Abreu Figueiredo, Jayne / Andrade Teixeira, Mariá / Henrique Campelo, Pedro / Maria Teixeira Lago, Amanda / Pereira de Souza, Tatiane / Irene Yoshida, Maria / Rodrigues de Oliveira, Cassiano / Paula Aparecida Pereira, Ana / Maria Pastore, Gláucia / Aparecido Sanches, Edgar / Alvarenga Botrel, Diego / Vilela Borges, Soraia

    Food research international (Ottawa, Ont.)

    2020  Volume 137, Page(s) 109563

    Abstract: ... controlled release at different temperatures (25 °C and 35 °C) were investigated. In contrast with the IN and OL ... a Fickian diffusion mechanism (n ≤ 0.43). The increase of temperature from 25 °C to 35 °C influenced ...

    Abstract Camu-camu (Myrciaria dubia [H.B.K] McVaugh) is a Amazonian fruit rich in ascorbic acid and phenolic compounds, and has been attracting great interest from the food, pharmaceutical and nutraceutical industries due to its potential health benefits. The bioactive compounds from camu-camu are considered sensitive and unstable, resulting in nutritional losses and impairment of its commercialization and export. For this reason, the camu-camu extract (pulp and peel) was subjected to microencapsulation by spray drying process using maltodextrin (MD), inulin (IN), and oligofructose (OL) as carrier agents. Lyophilized in natura camu-camu extract (CEL) was also evaluated. Thus, physicochemical and thermal properties and controlled release at different temperatures (25 °C and 35 °C) were investigated. In contrast with the IN and OL microparticles, the MD microparticles showed lower density and hygroscopicity, besides greater thermal stability, antioxidant activity, and retention of ascorbic acid and anthocyanins. FTIR spectra allowed the qualitative evidence of encapsulation of the bioactive compounds from the camu-camu extract. The highest percentage of volatile compounds was observed in IN microparticles, followed by OL and MD microparticles. The major group of compounds identified in CEL were terpenes (88%). The Korsmeyer-Peppas mathematical model allowed to describe the controlled release behavior of ascorbic acid and anthocyanins in the powder extracts. The controlled release followed a Fickian diffusion mechanism (n ≤ 0.43). The increase of temperature from 25 °C to 35 °C influenced on the release of bioactive compounds in all treatments, showing greater release for MD microparticles. The encapsulating materials were considered effective for the production of camu-camu extract powder, contributing to the better use of this Amazonian fruit. In addition, the encapsulation process increased the stability of its bioactive compounds, representing a tool to facilitate their incorporation in several matrices to act as antioxidant and coloring agents, as well as nutraceutical.
    MeSH term(s) Biopolymers ; Delayed-Action Preparations ; Myrtaceae ; Plant Extracts ; Prebiotics
    Chemical Substances Biopolymers ; Delayed-Action Preparations ; Plant Extracts ; Prebiotics
    Language English
    Publishing date 2020-07-25
    Publishing country Canada
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1111695-x
    ISSN 1873-7145 ; 0963-9969
    ISSN (online) 1873-7145
    ISSN 0963-9969
    DOI 10.1016/j.foodres.2020.109563
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  10. Article: Serum from Asthmatic Mice Potentiates the Therapeutic Effects of Mesenchymal Stromal Cells in Experimental Allergic Asthma.

    Abreu, Soraia C / Xisto, Debora G / de Oliveira, Tainá B / Blanco, Natalia G / de Castro, Lígia Lins / Kitoko, Jamil Zola / Olsen, Priscilla C / Lopes-Pacheco, Miquéias / Morales, Marcelo M / Weiss, Daniel J / Rocco, Patricia R M

    Stem cells translational medicine

    2018  Volume 8, Issue 3, Page(s) 301–312

    Abstract: Asthma is a chronic inflammatory disease characterized by airway inflammation and remodeling, which can lead to progressive decline of lung function. Although mesenchymal stromal cells (MSCs) have shown beneficial immunomodulatory properties in ... ...

    Abstract Asthma is a chronic inflammatory disease characterized by airway inflammation and remodeling, which can lead to progressive decline of lung function. Although mesenchymal stromal cells (MSCs) have shown beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been limited. Mounting evidence suggests that prior exposure of MSCs to specific inflammatory stimuli or environments can enhance their immunomodulatory properties. Therefore, we investigated whether stimulating MSCs with bronchoalveolar lavage fluid (BALF) or serum from asthmatic mice could potentiate their therapeutic properties in experimental asthma. In a house dust mite (HDM) extract asthma model in mice, unstimulated, asthmatic BALF-stimulated, or asthmatic serum-stimulated MSCs were administered intratracheally 24 hours after the final HDM challenge. Lung mechanics and histology; BALF protein, cellularity, and biomarker levels; and lymph-node and bone marrow cellularity were assessed. Compared with unstimulated or BALF-stimulated MSCs, serum-stimulated MSCs further reduced BALF levels of interleukin (IL)-4, IL-13, and eotaxin, total and differential cellularity in BALF, bone marrow and lymph nodes, and collagen fiber content, while increasing BALF IL-10 levels and improving lung function. Serum stimulation led to higher MSC apoptosis, expression of various mediators (transforming growth factor-β, interferon-γ, IL-10, tumor necrosis factor-α-stimulated gene 6 protein, indoleamine 2,3-dioxygenase-1, and IL-1 receptor antagonist), and polarization of macrophages to M2 phenotype. In conclusion, asthmatic serum may be a novel strategy to potentiate therapeutic effects of MSCs in experimental asthma, leading to further reductions in both inflammation and remodeling than can be achieved with unstimulated MSCs. Stem Cells Translational Medicine 2019;8:301&312.
    MeSH term(s) Animals ; Asthma/immunology ; Asthma/therapy ; Bronchoalveolar Lavage Fluid/immunology ; Disease Models, Animal ; Female ; Interleukin-10/immunology ; Interleukin-13/immunology ; Interleukin-4/immunology ; Lung/immunology ; Male ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/immunology ; Mice ; Mice, Inbred BALB C
    Chemical Substances Interleukin-13 ; Interleukin-10 (130068-27-8) ; Interleukin-4 (207137-56-2)
    Language English
    Publishing date 2018-11-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2642270-0
    ISSN 2157-6580 ; 2157-6564
    ISSN (online) 2157-6580
    ISSN 2157-6564
    DOI 10.1002/sctm.18-0056
    Database MEDical Literature Analysis and Retrieval System OnLINE

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