Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/50058
Title: Mesenchymal stromal cells-based therapy in a murine model of elastase-induced emphysema: Simvastatin as a potential adjuvant in cellular homing
Authors: Faria, Carolina Arruda de
Silva Júnior, Wilson Araújo
Coelho, Karoline Brito Caetano Andrade
Bassi, Mirian
Colombari, Eduardo
Zanette, Dalila Lucíola
Ribeiro-Paes, João Tadeu
Affilliation: Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Genética. Ribeirão Preto, SP, Brasil.
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Genética. Ribeirão Preto, SP, Brasil.
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Cirurgia e Anatomia. Ribeirão Preto, SP, Brasil.
Universidade Estadual Paulista. Faculdade de Odontologia. Departamento de Fisiologia e Patologia. Araraquara, SP, Brasil.
Universidade Estadual Paulista. Faculdade de Odontologia. Departamento de Fisiologia e Patologia. Araraquara, SP, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologias Aplicadas em Saúde. Curitiba, PR, Brasil.
Universidade Estadual Paulista. Departamento de Biotecnologia. ASSIS, SP, Brasil.
Abstract: Chronic Obstructive Pulmonary Disease - COPD is characterized by the destruction of alveolar walls associated to a chronic inflammatory response of the airways. There is no clinical therapy for COPD. In this context, cell-based therapies represent a promising therapeutic approach for chronic lung disease. The goal of this work was to evaluate the effect of simvastatin on cell-based therapy in a mice emphysema model. Female FVB mice received intranasal instillation of elastase (three consecutive doses of 50 μL) in order to promote pulmonary emphysema. After 21 days of the first instillation, the animals were treated with Adipose-Derived Mesenchymal Stromal Cells (AD-MSC, 2.6 × 106 ) via retro-orbital infusion associated or not with simvastatin administrated daily via oral gavage (15 mg/kg/15d). Before and after these treatments, the histological and morphometrical analyses of the lung tissue, as so as lung function (whole body plethysmography) were evaluated. PAI-1 gene expression, an upregulated factor by ischemia that indicate a low survival of transplanted MSC, was also evaluated. The result regarding morphological and functional aspects of both lungs, presented no significant difference among the groups (AD-MSC or AD-MSC + Simvastatin). However, significant anatomical difference was observed in the right lung of the both groups of mice. The results shown a higher deposition of cells in the right lung, with might to be explained by anatomical differences (slightly higher right bronchi). Decreased levels of PAI-1 were observed in the simvastatin treated groups. The pulmonary ventilation was similar between the groups with only a tendency to a lower in the elastase treated animals due to a low respiratory frequency. In conclusion, the results suggest that both AD-MSC and simvastatin treatments could promote an improvement of morphological recovery of pulmonary emphysema, that it was more pronounced in the right lung.
Keywords: Chronic Obstructive Pulmonary Disease
Cell- and Tissue-Based Therapy
Mesenchymal Stem Cells
Simvastatin
???metadata.dc.subject.fr???: Broncho-pneumopathie chronique obstructive
Thérapie cellulaire et tissulaire
Cellules souches mésenchymateuses
Simvastatine
Keywords in spanish: Enfermedad Pulmonar Obstructiva Crónica
Tratamiento Basado en Trasplante de Células y Tejidos
Células Madre Mesenquimatosas
Simvastatina
keywords: COPD
Terapia Celular
MSC
Sinvastatina
DeCS: Doença Pulmonar Obstrutiva Crônica
Terapia Baseada em Transplante de Células e Tecidos
Células-Tronco Mesenquimais
Issue Date: 2021
Publisher: Elsevier. Academic Press
Citation: FARIA, Carolina Arruda de et al. Mesenchymal stromal cells-based therapy in a murine model of elastase-induced emphysema: Simvastatin as a potential adjuvant in cellular homing. Pulmonary Pharmacology & Therapeutics. v. 70, n. 102075, p. 1–10, 2021.
DOI: 10.1016/j.pupt.2021.102075
ISSN: 0009-2797
Copyright: open access
Appears in Collections:PR - ICC - Artigos de Periódicos
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