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Intratracheal instillation of bone marrow-derived cell in an experimental model of silicosis
Roberta M Lassance1, Luiz Felipe M Prota, Tatiana Maron-Gutierrez
1Laboratory of Cellular and Molecular Physiology, Brazil.
Abstract:
The time course of lung mechanics, histology, and inflammatory and fibrogenic mediators are analysed after intratracheal instillation (IT) of bone marrow-derived cells (BMDC) in a model of silicosis. C57BL/6 mice were randomly divided into SIL (silica, 20mg IT) and control (CTRL) groups (saline IT). At day 15, mice received saline or BMDC (2 x 10(6)cells) IT. The biodistribution of technetium-99m BMDC was higher in lungs compared with other organs. At days 30 and 60, lung mechanics, the area of granulomatous nodules, and mRNA expression of IL-1beta and TGF-beta were higher in SIL than CTRL animals. BMDC minimized changes in lung mechanics, the area of granulomatous nodules, and total cell infiltration at day 30, but these effects were no longer observed at day 60. Conversely, BMDC avoided the expression of IL-1beta at days 30 and 60 and TGF-beta only at day 30. In conclusion, BMDC therapy improved lung mechanics and histology, but this beneficial effect was not maintained in the course of injury.
Insights
Bone marrow-derived cells (BMDC) temporarily improved lung function and reduced silicosis markers in mice. However, these beneficial effects on lung mechanics and histology were not sustained long-term.
Area of Science:
- Pulmonary toxicology
- Cell therapy
- Immunology
Background:
- Silicosis is a progressive lung disease caused by silica dust inhalation.
- Current treatments for silicosis are limited, necessitating research into novel therapeutic approaches.
- Bone marrow-derived cells (BMDC) show potential for tissue repair and immunomodulation.
Purpose of the Study:
- To investigate the therapeutic potential of intratracheal instillation of BMDC in a mouse model of silicosis.
- To evaluate the effects of BMDC on lung mechanics, histology, and inflammatory mediators over time.
- To assess the biodistribution and efficacy of BMDC in mitigating silica-induced lung injury.
Main Methods:
- C57BL/6 mice were induced with silicosis via silica IT, followed by saline or BMDC treatment.
- Lung mechanics, histology, and mRNA expression of IL-1beta and TGF-beta were assessed at days 30 and 60.
- Biodistribution of 99mTc-labeled BMDC was analyzed.
Main Results:
- BMDC treatment transiently improved lung mechanics and reduced granulomatous nodule area and cell infiltration at day 30.
- Silicosis model showed increased lung mechanics, nodule area, and IL-1beta/TGF-beta mRNA expression at days 30 and 60.
- BMDC administration reduced IL-1beta expression at both time points and TGF-beta at day 30, but these effects diminished by day 60.
Conclusions:
- BMDC therapy offers short-term benefits in improving lung mechanics and histology in silicosis.
- The therapeutic effects of BMDC in silicosis are not sustained beyond 30 days post-treatment.
- Further research is needed to enhance the persistence and efficacy of BMDC for chronic lung diseases like silicosis.
