hMSCs suppress neutrophil-dominant airway inflammation in a murine model of asthma

Although chronic eosinophilic inflammation is a common feature in patients with asthma, some patients have neutrophil-dominant inflammation, which is known to be associated with severe asthma.Human mesenchymal stem cells (hMSCs) have shown promise in treating various refractory immunological diseases. Thus, hMSCs may represent an alternative therapeutic option for asthma patients with neutrophil-dominant inflammation, in whom current treatments are ineffective. BALB/c mice exposed to ovalbumin and polyinosinic:polycytidylic acid (Poly I:C) to induce neutrophilic airway inflammation were systemically treated with hMSCs to examine whether the hMSCs can modulate neutrophilic airway inflammation. In addition, cytokine production was evaluated in co-cultures of hMSCs with either anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) obtained from asthmatic patients or cells of the human bronchial epithelial cell line BEAS-2B to assess the response to hMSC treatment. The total number of immune cells in bronchoalveolar lavage fluid (BALF) showed a dramatic decrease in hMSC-treated asthmatic mice, and, in particular, neutrophilic infiltration was significantly attenuated. This phenomenon was accompanied by reduced CXCL15 production in the BALF. BEAS-2B cells co-cultured with hMSCs showed reduced secretion of IL-8. Moreover, decreased secretion of IL-4, IL-13 and IFN-γ was observed when human PBMCs were cultured with hMSCs, whereas IL-10 production was greatly enhanced. Our data imply that hMSCs may have a role in reducing neutrophilic airway inflammation by downregulating neutrophil chemokine production and modulating T-cell responses. Human stem cells derived from umbilical cord blood reduce lung inflammation in a mouse model of severe asthma. A hallmark of asthma is airway inflammation triggered by specific white blood cells (eosinophils and neutrophils) in the lungs. Eosinophil-mediated inflammation is responsive to inhaled corticosteroids, but neutrophil-predominant inflammation is harder to treat with available anti-asthmatics. You Sook Cho at the University of Ulsan College of Medicine, Seoul, and colleagues have shown that injecting these stem cells into mice with neutrophilic airway inflammation significantly decreased the number of neutrophils in the lungs. The stem cells dampen the inflammatory response by reducing the production and release of key pro-inflammatory molecules from peripheral blood white (mononuclear) cells from patients with severe asthma and from human bronchial epithelial cells. These results suggest a potential new approach for managing refractory cases.