Protective effects of bone marrow mononuclear cell therapy on lung and heart in an elastase-induced emphysema model

Abstract

We hypothesized that bone marrow-derived mononuclear cell (BMDMC) therapy protects the lung and consequently the heart in experimental elastase-induced emphysema. Twenty-four female C57BL/6 mice were intratracheally instilled with saline (C group) or porcine pancreatic elastase (E group) once a week during 4 weeks. C and E groups were randomized into subgroups receiving saline (SAL) or male BMDMCs (2 × 10(6), CELL) intravenously 3h after the first saline or elastase instillation. Compared to E-SAL group, E-CELL mice showed, at 5 weeks: lower mean linear intercept, neutrophil infiltration, elastolysis, collagen fiber deposition in alveolar septa and pulmonary vessel wall, lung cell apoptosis, right ventricle wall thickness and area, higher endothelial growth factor and insulin-like growth factor mRNA expressions in lung tissue, and reduced platelet-derived growth factor, transforming growth factor-β, and caspase-3 expressions. In conclusion, BMDMC therapy was effective at modulating the inflammatory and remodeling processes in the present model of elastase-induced emphysema.

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

“…Furthermore, IL-1β has been implicated in fibroblast activation and collagen deposition [33]. As already demonstrated in other models of lung inflammation and fibrosis [10], BMDCs were able to prevent an increase in the amount of TGF-β in lung tissue as well as TGF-β mRNA after instillation of silica [3]. TGF-β regulates a wide variety of cellular processes including cell growth, apoptosis, differentiation, migration, and extracellular matrix production [34].…”

“…Several studies have reported on the beneficial effects of bone marrow cell therapy in different models of lung injury [5,6,7,8,9,10]. In experimental models of lung fibrosis, bone marrow-derived cells (BMDCs) were able to repair damaged tissue by modulating the inflammatory process and replacing damaged cells [3,5,6,7].…”

CD11b+ and Sca-1+ Cells Exert the Main Beneficial Effects of Systemically Administered Bone Marrow-Derived Mononuclear Cells in a Murine Model of Mixed Th2/Th17 Allergic Airway Inflammation

“…Furthermore, it is imperative to understand which cell populations in the BMDMCs might convey beneficial effects for use in any given disease. In preclinical models of lung diseases, BMDMCs have been shown to abrogate airway inflammation and remodeling and to promote lung repair in mouse models of acute lung injury, chronic obstructive pulmonary disorder, silicosis and asthma [24–26, 32, 36, 58]. With respect to asthma, we have previously compared BMDMCs with MSCs in a mild Th2-mediated eosinophilic allergic airway disease induced by ovalbumin sensitization and challenge [12].…”

“…Thus, either a small number of MSCs (i.e., the approximately 5 × 10 4 MSCs contained in the BMDMCs) was sufficient to mitigate the effect or another cell type in the BMDMC also played a role. Previous studies in other disease models have suggested that the functional effects of the BMDMCs result from a balance between different cell types, with potential beneficial involvement of all component cells [24–26, 32, 36, 52, 53, 57, 58]. BMDMCs include a variety of cells: progenitor cells (hematopoietic progenitor cells and mesenchymal stromal cells), leukocytes (B and T lymphocytes, and monocytes/macrophages), and endothelial cells.…”

“…As previously described, animals received either HLFs ( n = 6), mMSCs ( n = 6), BMDMCs ( n = 13), or BMDMCs depleted of either CD45 ( n = 6), CD34 ( n = 6), CD3 ( n = 6), CD19 ( n = 6), CD11b ( n = 9), CD31 ( n = 6), or Sca-1 ( n = 6) cells (Fig. 1B) [16, 19, 20, 24, 25, 35, 36]. …”