Intratracheal instillation of bone marrow-derived cell in an experimental model of silicosis

Lassance, Roberta M.; Prota, Luiz Felipe M.; Maron‐Gutierrez, Tatiana; Garcia, Cristiane Sousa Nascimento Baez; Abreu, Soraia C.; Pássaro, Caroline P.; Xisto, Débora G.; Castiglione, Raquel C.; Carreira, Humberto; Ornellas, Débora S.; Santana, Maria Cristina E.; Souza, Sérgio Augusto Lopes de; Gutfilen, Bianca; Fonseca, Leila S.; Rocco, Patrícia Rieken Macêdo; Morales, Marcelo M.

doi:10.1016/j.resp.2009.09.004

Cited by 32 publications

(28 citation statements)

References 31 publications

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“…The relative amount of total DNA was calculated as a ratio (2-DC t ) of Sry and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The primers for GAPDH were: forward: 59-CCACCAACT GCTTAGCCC-39; reverse; 59-GACACCTACAAAGAAGGGT CCA-39, 145 bp [8].…”

Section: Y Chromosome Dna Detectionmentioning

confidence: 99%

“…All these studies described an engraftment lower than 5% [5,6]. In this context, LASSANCE et al [8] reported that intratracheal instillation of BMDCs improved lung mechanics and histology independent of the ability of cells to engraft in the lung in a murine model of silicosis. In silicotic animals, the use of fluorescent techniques to evaluate homing, such as green fluorescent protein-positive cells and fluorescence in situ hybridisation analysis, is not feasible because silica crystal is highly birefringent.…”

Section: Lung Cell Biology T Maron-gutierrez Et Almentioning

confidence: 99%

“…Recently, we analysed the role of intratracheal instillation of BMDC in a model of silicosis and observed only a mild improvement in lung mechanics [8], which may be attributed to: 1) the pathogenesis of silicosis; 2) the timing of BMDC injection (early or late in the course of lung injury); and 3) the type of cell and route of administration. Therefore, we tested the hypothesis that early, intravenous and a single dose of bone marrowderived mononuclear cells (BMDMC) may avoid mechanical changes in the lung in a murine model of silica-induced fibrosis.…”

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Bone marrow-derived mononuclear cell therapy attenuates silica-induced lung fibrosis

Maron‐Gutierrez¹,

Castiglione²,

Xisto³

et al. 2010

Eur Respir J

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This study tests the hypothesis that bone marrow-derived mononuclear cell (BMDMC) therapy may reduce lung inflammation and fibrosis leading to an improvement in respiratory mechanics in a murine model of silicosis.52 female C57BL/6 mice were randomly assigned into four groups. In the silica group (SIL), silica suspension (20 mg/50 mL in saline) was intratracheally instilled. In the control animals, 50 mL saline was administered intratracheally. At 1 h, the control and SIL groups were further randomised, receiving BMDMC (2610 6 In the SIL-cell group, the fraction area of granuloma, the number of macrophages and the collagen fibre content were reduced, yielding improved lung mechanics. The presence of male donor cells in lung tissue was not confirmed using detection of Y chromosome DNA. Nevertheless, caspase-3, IL-1b, IL-1a, IL-1RN and TGF-b mRNA expression diminished after cell therapy.In conclusion, BMDMC acted on inflammatory and fibrogenic processes improving lung function through paracrine effects.

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Section: Y Chromosome Dna Detectionmentioning

confidence: 99%

Section: Lung Cell Biology T Maron-gutierrez Et Almentioning

confidence: 99%

mentioning

confidence: 99%

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Bone marrow-derived mononuclear cell therapy attenuates silica-induced lung fibrosis

Maron‐Gutierrez¹,

Castiglione²,

Xisto³

et al. 2010

Eur Respir J

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“…In a previous study, we observed that in experimental silicosis, the early beneficial effects of BMDC therapy on lung inflammation and mechanics were transient [11]. Therefore, we tested the hypothesis that a protocol with repeated intratracheal administration of BMDCs could reduce the ongoing inflammatory and fibroelastogenic processes, thus improving lung mechanics.…”

Section: Introductionmentioning

confidence: 99%

Repeated Administration of Bone Marrow-Derived Cells Prevents Disease Progression in Experimental Silicosis

Lopes‐Pacheco

Xisto

Ornellas

et al. 2013

Cell Physiol Biochem

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Background/Aims: Bone marrow-derived cells (BMDCs) reduced mechanical and histologic changes in the lung in a murine model of silicosis, but these beneficial effects did not persist in the course of lung injury. We hypothesized that repeated administration of BMDCs may decrease lung inflammation and remodeling thus preventing disease progression. Methods: One hundred and two C57BL/6 mice were randomly divided into SIL (silica, 20 mg intratracheally [IT]) and control (C) groups (saline, IT). C and SIL groups were further randomized to receive BMDCs (2×10⁶ cells) or saline IT 15 and 30 days after the start of the protocol. Results: By day 60, BMDCs had decreased the fractional area of granuloma and the number of polymorphonuclear cells, macrophages (total and M1 phenotype), apoptotic cells, the level of transforming growth factor (TGF)-β‚ and types I and III collagen fiber content in the granuloma. In the alveolar septa, BMDCs reduced the amount of collagen and elastic fibers, TGF-β, and the number of M1 and apoptotic cells. Furthermore, interleukin (IL)-1β, IL-1R1, caspase-3 mRNA levels decreased and the level of IL-1RN mRNA increased. Lung mechanics improved after BMDC therapy. The presence of male donor cells in lung tissue was not observed using detection of Y chromosome DNA. Conclusion: repeated administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis, thus improving lung mechanics through the release of paracrine factors.

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“…Other studies have been carried out using stem cell transplantation (either mesenchymal cells or cells derived from fetal membranes of human term placenta) in animal models in which lung fibrosis has been induced by bleomycin and also by silica [26,[33][34][35][36]. These cells were found to express alveolar epithelium markers after injection into mice and to exert significant antiinflammatory and anti-fibrotic effects in the bleomycin as well as in the silica models of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Rescue of murine silica-induced lung injury and fibrosis by human embryonic stem cells

et al. 2011

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Alveolar type II pneumocytes (ATII cells) are considered putative alveolar stem cells. Since no treatment is available to repair damaged epithelium and prevent lung fibrosis, novel approaches to induce regeneration of injured alveolar epithelium are desired.The objective of this study was to assess both the capacity of human embryonic stem cells (HUES-3) to differentiate in vitro into ATII cells and the ability of committed HUES-3 cells (HUES-3-ATII cells) to recover in vivo a pulmonary fibrosis model obtained by silica-induced damage.In vitro differentiated HUES-3-ATII cells displayed an alveolar phenotype characterised by multilamellar body and tight junction formation, by the expression of specific markers such as surfactant protein (SP)-B, SP-C and zonula occludens (ZO)-1 and the activity of cystic fibrosis transmembrane conductance regulator-mediated chloride ion transport.After transplantation of HUES-3-ATII cells into silica-damaged mice, histological and biomolecular analyses revealed a significant reduction of inflammation and fibrosis markers along with lung function improvement, weight recovery and increased survival. The persistence of human SP-C, human nuclear antigen and human DNA in the engrafted lungs indicates that differentiated cells remained engrafted up to 10 weeks.In conclusion, cell therapy using HUES-3 cells may be considered a promising approach to lung injury repair.

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Intratracheal instillation of bone marrow-derived cell in an experimental model of silicosis

Cited by 32 publications

References 31 publications

Bone marrow-derived mononuclear cell therapy attenuates silica-induced lung fibrosis

Bone marrow-derived mononuclear cell therapy attenuates silica-induced lung fibrosis

Repeated Administration of Bone Marrow-Derived Cells Prevents Disease Progression in Experimental Silicosis

Rescue of murine silica-induced lung injury and fibrosis by human embryonic stem cells

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