Systemic human orbital fat-derived stem/stromal cell transplantation ameliorates acute inflammation in lipopolysaccharide-induced acute lung injury

Objective: Acute lung injury results in acute respiratory distress syndrome. There is no standard therapy for acute respiratory distress syndrome but supportive care. Stem cells offer a new therapeutic potential for tissue regeneration as a result of their self-renewal, multipotency, and paracrine capabilities. The objective of this study is to investigate the effects and the mechanisms of systemic human orbital fat-derived stem/stromal cell transplantation on lipopolysaccharide-induced acute lung injury. Design: Prospective, randomized, controlled study. Setting: University-affiliated research institute. Subjects: Male BALB/c mice. Interventions: Twenty-five micrograms lipopolysaccharide in 50 μL sterile saline or 50 μL of sterile saline was delivered through intratracheal injection. Twenty mins later, the animals were further randomized into subgroups that received either a tail vein injection of 3 × 10⁵ orbital fat-derived stem/stromal cells in 50 μL phosphate-buffered saline or 50 μL phosphate-buffered saline. Measurements and Main Results: Low immunogenicity and immune-tolerated of orbital fat-derived stem/stromal cells were observed in this xenotransplanted model. Orbital fat-derived stem/stromal cells significantly reduced lipopolysaccharide-induced pulmonary inflammation, which was evidenced by a decrease in total protein concentration and neutrophil counts in alveolar fluid through bronchoalveolar lavage, reduced endothelial and alveolar epithelial permeability as well as neutrophil (Ly6G-expressing cells) and macrophage (CD68-expressing cells) infiltration. Lipopolysaccharide-induced expression of CD14, inducible nitric oxide synthase, and transforming growth factor-β in lung tissue was significantly inhibited by orbital fat-derived stem/stromal cells. Orbital fat-derived stem/stromal cells not only reduced the circulation numbers of macrophages and neutrophils (CD11b-expressing cells), but also decreased systemic proinflammatory chemokine levels such as macrophage inflammatory protein-1-γ, B-lymphocyte chemoattractant, interleukin-12, and subsequent circulation helper T cell (CD4-expressing cells) numbers. Furthermore, few human orbital fat-derived stem/stromal cells were detectable in the recipient lung after acute inflammation subsided. Conclusions: Systemic orbital fat-derived stem/stromal cell transplantation was effective in modulating inflammation during acute lung injury. The therapeutic effect was attributed to the inhibition of acute inflammatory responses.