Bone Marrow-Derived Cells Participate in Stromal Remodeling of the Lung Following Acute Bacterial Pneumonia in Mice

Abstract

Bone marrow-derived cells (BMDC) have been shown to graft injured tissues, differentiate in specialized cells, and participate in repair. The importance of these processes in acute lung bacterial inflammation and development of fibrosis is unknown. The goal of this study was to investigate the temporal sequence and lineage commitment of BMDC in mouse lungs injured by bacterial pneumonia. We transplanted GFP-tagged BMDC into 5-Gy-irradiated C57BL/6 mice. After 3 months of recovery, mice were subjected to LD 50 intratracheal instillation of live E. coli (controls received saline) which produced pneumonia and subsequent areas of fibrosis. Lungs were investigated by immunohistology for up to 6 months. At the peak of lung inflammation, the predominant influx of BMDC were GFP + leukocytes. Postinflammatory foci of lung fibrosis were evident after 1-2 months. The fibrotic foci in lung stroma contained clusters of GFP + CD45 + cells, GFP + vimentin-positive cells, and GFP + collagen I-positive fibroblasts. GFP + endothelial or epithelial cells were not identified. These data suggest that following 5-Gy irradiation and acute bacterial pneumonia, BMDC may temporarily participate in lung postinflammatory repair and stromal remodeling without long-term engraftment as specialized endothelial or epithelial cells.

Oxidative stress, DNA methylation, and telomere length changes in peripheral blood mononuclear cells after pulmonary exposure to metal-rich welding nanoparticles

“…As the response subsided, PBMC telomere length ratio in the MMA-SS group returned to control levels at 3 and 10 d before increasing at 30 d, suggesting either a biphasic response or changes in cell populations. In other types of lung injury, bone marrow-derived progenitor cells have been observed to move into the lungs and are involved in lung repair (Serikov et al, 2008; Yamada et al, 2004). The influx of bone marrow-derived, stem-like cells may have altered overall telomere length.…”

Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model

“…In our initial observation, we defined the beneficial effects of the systemic administration of mesenchymal stem cells to control ARDS mainly by their anti-inflammatory properties. Multiple groups have reported similar observations where the protective effect has been demonstrated in different animal models and human ex-vivo lungs [17-22]. The protective effects of mesenchymal stem cells are attributed to several mechanisms including secretion of the anti-inflammatory cytokines IL-10 and TGF-β, and Keratinocyte Growth Factor (KGF) and elaboration of antibacterial peptides.…”

Mesenchymal stem cells: mechanisms of potential therapeutic benefit in ARDS and sepsis

“…13,24 A growing number of studies have shown that MSCs have immunomodulatory and anti-infl ammatory eff ects despite minimum or absent engraftment. [25][26][27][28] Consequently, research has shifted towards identifi cation of alternative pathways through which MSCs interact with host tissue, including interactions between cells, direct interactions with the host immune system, and mitochondrial transfer. The pathway with the most robust supporting evidence is the ability of MSCs to coordinate tissue repair through the release of soluble paracrine factors.…”