1. Intratracheal Administration of Autologous Bone Marrow-Derived Cells Ameliorates Monocrotaline-Induced Pulmonary Vessel Remodeling and Lung Inflammation in Rats.
- Author
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Yamazato, Yoriko, Yamazato, Masanobu, Ishida, Akio, Fujita, Jiro, and Ohya, Yusuke
- Subjects
CYTOKINES ,BONE marrow diseases ,ALVEOLAR macrophages ,MESENCHYMAL stem cells ,MACROPHAGES ,THERAPEUTICS - Abstract
Purpose: Inflammation is a feature of lung injury and plays a critical role in pulmonary vascular remodeling. Bone marrow-derived cells (BMCs) have anti-inflammatory properties and favor macrophage differentiation into an alternatively activated regulatory M2 profile. We investigated the effect of autologous BMCs on monocrotaline-induced pulmonary vessel remodeling and lung inflammation in rats, by direct administration into lungs via the airway.Methods: BMCs were isolated and plastic-adherent cells were cultured for 3 weeks. 1 week following monocrotaline (60 mg/kg) treatment, fluorescently labeled autologous BMCs (1 × 10
6 cells) or vehicle were administered intratracheally to male Sprague-Dawley rats. 4 weeks following monocrotaline treatment, lung pathology was evaluated.Results: Monocrotaline increased pulmonary vessel wall thickness, perivascular infiltration, alveolar septal thickening, and inflammatory cell infiltration including T lymphocytes and monocytes/macrophages in alveolar areas, and also increased mRNA expression of inflammatory-related cytokines including IL-10 in the lung. Intratracheal administration of autologous BMCs prevented pulmonary vessel wall thickening and perivascular infiltration, and increased CD163-positive M2-like macrophages in perivascular areas. BMC administration inhibited the thickening of alveolar septa and reduced monocrotaline-induced inflammatory cell infiltration in lung parenchyma compared with monocrotaline-vehicle-treated-rats. Furthermore, BMCs administration increased expression of CD163-positive cells in perivascular areas and maintained the increased mRNA expression of IL-10.Conclusions: Intratracheal administration of autologous BMCs prevented monocrotaline-induced pulmonary vessel remodeling and lung inflammation, at least in part, through induction of alternatively activated macrophages and regulation of the local lung environment toward resolving inflammation. [ABSTRACT FROM AUTHOR]- Published
- 2018
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