Lung Tissue Damage Associated with Allergic Asthma in BALB/c Mice Could Be Controlled with a Single Injection of Mesenchymal Stem Cells from Human Bone Marrow up to 14 d After Transplantation

Mesenchymal stem cell (MSC) research has demonstrated the potential of these cells to modulate lung inflammatory processes and tissue repair; however, the underlying mechanisms and treatment durability remain unknown. Here, we investigated the therapeutic potential of human bone marrow-derived MSCs...

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Main Authors: Lidiane Maria Boldrini-Leite, Pedro Vicente Michelotto, Sérgio Adriane Bezerra de Moura, Luiz Guilherme Achcar Capriglione, Fernanda Cristina Mendes Barussi, Felipe Yukio Ishikawa Fragoso, Alexandra Cristina Senegaglia, Paulo Roberto Slud Brofman
Format: Article
Language:English
Published: SAGE Publishing 2020-03-01
Series:Cell Transplantation
Online Access:https://doi.org/10.1177/0963689720913254
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spelling doaj-4207d4c6ef6e4618bf5692e4fa880f6e2020-11-25T03:26:29ZengSAGE PublishingCell Transplantation1555-38922020-03-012910.1177/0963689720913254Lung Tissue Damage Associated with Allergic Asthma in BALB/c Mice Could Be Controlled with a Single Injection of Mesenchymal Stem Cells from Human Bone Marrow up to 14 d After TransplantationLidiane Maria Boldrini-Leite0Pedro Vicente Michelotto1Sérgio Adriane Bezerra de Moura2Luiz Guilherme Achcar Capriglione3Fernanda Cristina Mendes Barussi4Felipe Yukio Ishikawa Fragoso5Alexandra Cristina Senegaglia6Paulo Roberto Slud Brofman7 Core for Cell Technology, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil Department of Animal Science, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil Department of Morphology, Campus Universitário Lagoa Nova, Universidade Federal do Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil Core for Cell Technology, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil Department of Animal Science, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil Core for Cell Technology, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil Core for Cell Technology, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil Core for Cell Technology, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, BrazilMesenchymal stem cell (MSC) research has demonstrated the potential of these cells to modulate lung inflammatory processes and tissue repair; however, the underlying mechanisms and treatment durability remain unknown. Here, we investigated the therapeutic potential of human bone marrow-derived MSCs in the inflammatory process and pulmonary remodeling of asthmatic BALB/c mice up to 14 d after transplantation. Our study used ovalbumin to induce allergic asthma in male BALB/c mice. MSCs were injected intratracheally in the asthma groups. Bronchoalveolar lavage fluid (BALF) was collected, and cytology was performed to measure the total protein, hydrogen peroxide (H 2 O 2 ), and proinflammatory (IL-5, IL-13, and IL-17A) and anti-inflammatory (IL-10) interleukin (IL) levels. The lungs were removed for the histopathological evaluation. On day zero, the eosinophil and lymphochte percentages, total protein concentrations, and IL-13 and IL-17A levels in the BALF were significantly increased in the asthma group, proving the efficacy of the experimental model of allergic asthma. On day 7, the MSC-treated group exhibited significant reductions in the eosinophil, lymphocyte, total protein, H 2 O 2 , IL-5, IL-13, and IL-17A levels in the BALF, while the IL-10 levels were significantly increased. On day 14, the total cell numbers and lymphocyte, total protein, IL-13, and IL-17A levels in the BALF in the MSC-treated group were significantly decreased. A significant decrease in airway remodeling was observed on days 7 and 14 in almost all bronchioles, which showed reduced inflammatory infiltration, collagen deposition, muscle and epithelial thickening, and mucus production. These results demonstrate that treatment with a single injection of MSCs reduces the pathophysiological events occurring in an experimental model of allergic asthma by controlling the inflammatory process up to 14 d after transplantation.https://doi.org/10.1177/0963689720913254
collection DOAJ
language English
format Article
sources DOAJ
author Lidiane Maria Boldrini-Leite
Pedro Vicente Michelotto
Sérgio Adriane Bezerra de Moura
Luiz Guilherme Achcar Capriglione
Fernanda Cristina Mendes Barussi
Felipe Yukio Ishikawa Fragoso
Alexandra Cristina Senegaglia
Paulo Roberto Slud Brofman
spellingShingle Lidiane Maria Boldrini-Leite
Pedro Vicente Michelotto
Sérgio Adriane Bezerra de Moura
Luiz Guilherme Achcar Capriglione
Fernanda Cristina Mendes Barussi
Felipe Yukio Ishikawa Fragoso
Alexandra Cristina Senegaglia
Paulo Roberto Slud Brofman
Lung Tissue Damage Associated with Allergic Asthma in BALB/c Mice Could Be Controlled with a Single Injection of Mesenchymal Stem Cells from Human Bone Marrow up to 14 d After Transplantation
Cell Transplantation
author_facet Lidiane Maria Boldrini-Leite
Pedro Vicente Michelotto
Sérgio Adriane Bezerra de Moura
Luiz Guilherme Achcar Capriglione
Fernanda Cristina Mendes Barussi
Felipe Yukio Ishikawa Fragoso
Alexandra Cristina Senegaglia
Paulo Roberto Slud Brofman
author_sort Lidiane Maria Boldrini-Leite
title Lung Tissue Damage Associated with Allergic Asthma in BALB/c Mice Could Be Controlled with a Single Injection of Mesenchymal Stem Cells from Human Bone Marrow up to 14 d After Transplantation
title_short Lung Tissue Damage Associated with Allergic Asthma in BALB/c Mice Could Be Controlled with a Single Injection of Mesenchymal Stem Cells from Human Bone Marrow up to 14 d After Transplantation
title_full Lung Tissue Damage Associated with Allergic Asthma in BALB/c Mice Could Be Controlled with a Single Injection of Mesenchymal Stem Cells from Human Bone Marrow up to 14 d After Transplantation
title_fullStr Lung Tissue Damage Associated with Allergic Asthma in BALB/c Mice Could Be Controlled with a Single Injection of Mesenchymal Stem Cells from Human Bone Marrow up to 14 d After Transplantation
title_full_unstemmed Lung Tissue Damage Associated with Allergic Asthma in BALB/c Mice Could Be Controlled with a Single Injection of Mesenchymal Stem Cells from Human Bone Marrow up to 14 d After Transplantation
title_sort lung tissue damage associated with allergic asthma in balb/c mice could be controlled with a single injection of mesenchymal stem cells from human bone marrow up to 14 d after transplantation
publisher SAGE Publishing
series Cell Transplantation
issn 1555-3892
publishDate 2020-03-01
description Mesenchymal stem cell (MSC) research has demonstrated the potential of these cells to modulate lung inflammatory processes and tissue repair; however, the underlying mechanisms and treatment durability remain unknown. Here, we investigated the therapeutic potential of human bone marrow-derived MSCs in the inflammatory process and pulmonary remodeling of asthmatic BALB/c mice up to 14 d after transplantation. Our study used ovalbumin to induce allergic asthma in male BALB/c mice. MSCs were injected intratracheally in the asthma groups. Bronchoalveolar lavage fluid (BALF) was collected, and cytology was performed to measure the total protein, hydrogen peroxide (H 2 O 2 ), and proinflammatory (IL-5, IL-13, and IL-17A) and anti-inflammatory (IL-10) interleukin (IL) levels. The lungs were removed for the histopathological evaluation. On day zero, the eosinophil and lymphochte percentages, total protein concentrations, and IL-13 and IL-17A levels in the BALF were significantly increased in the asthma group, proving the efficacy of the experimental model of allergic asthma. On day 7, the MSC-treated group exhibited significant reductions in the eosinophil, lymphocyte, total protein, H 2 O 2 , IL-5, IL-13, and IL-17A levels in the BALF, while the IL-10 levels were significantly increased. On day 14, the total cell numbers and lymphocyte, total protein, IL-13, and IL-17A levels in the BALF in the MSC-treated group were significantly decreased. A significant decrease in airway remodeling was observed on days 7 and 14 in almost all bronchioles, which showed reduced inflammatory infiltration, collagen deposition, muscle and epithelial thickening, and mucus production. These results demonstrate that treatment with a single injection of MSCs reduces the pathophysiological events occurring in an experimental model of allergic asthma by controlling the inflammatory process up to 14 d after transplantation.
url https://doi.org/10.1177/0963689720913254
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