Human pluripotent stem cell-derived mesenchymal stem cells prevent allergic airway inflammation in mice

Abstract

We previously found that mesenchymal stem cells (MSCs) derived from human‐induced pluripotent stem cells (iPSCs) exerted immunomodulatory effects on Th2‐mediated allergic rhinitis in vitro. However, their contribution to the asthma and allergic rhinitis in animal models remains unclear. In this study, we developed a mouse model of ovalbumin (OVA)‐induced allergic inflammation in both the upper and lower airways and evaluated the effects of the systemic administration of human iPSC‐MSCs and bone marrow‐derived MSCs (BM‐MSCs) on allergic inflammation. Our results showed that treatments with both the iPSC‐MSCs and BM‐MSCs before the challenge phase protected the animals from the majority of allergy‐specific pathological changes. This protection included an inhibition of inflammatory cell infiltration and mucus production in the lung, a reduction in eosinophil infiltration in the nose, and a decrease in inflammatory cell infiltration in both the bronchoalveolar and nasal lavage fluids. In addition, treatment with iPSC‐MSCs or BM‐MSCs before the challenge phase resulted in reduced serum levels of Th2 immunoglobulins (e.g., IgE) and decreased levels of Th2 cytokines including interleukin (IL)‐4, IL‐5, or IL‐13 in the bronchoalveolar and/or nasal lavage fluids. Similar therapeutic effects were observed when the animals were pretreated with human iPSC‐MSCs before the sensitization phase. These data suggest that iPSC‐MSCs may be used as an alternative strategy to adult MSCs in the treatment of asthma and allergic rhinitis.