Mesenchymal stromal cells reduce house dust mite induced allergic airway inflammation in a humanised MIF expressing mouse model

Abstract

Mesenchymal stromal cells (MSCs) are a subset of bone-marrow derived cells with cytoprotective and immunomodulatory capabilities. Clinical trials are currently examining MSCs as a potential novel therapeutic approach to protect against injury perpetrated by an over-zealous immune response in a range of inflammatory conditions. Our previous research has identified the need for MSCs to be activated by pro-inflammatory signals to facilitate or enhance their therapeutic efficacy. High expression levels of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) are present in a range of inflammatory diseases including severe asthma. This study sought to elucidate the influence that MIF licensing has on human MSC cytoprotection and immune modulation in vitro. Moreover, the effect of MIF on MSCs therapeutic efficacy in vivo was investigated using a clinically relevant acute house dust mite (HDM) (Dermatophagoides pteronyssinus) model of allergic airway inflammation in humanised MIF mice. MIF pre-stimulation enhanced MSC promotion of wound healing in airway epithelial cells in a VEGF dependent manner. Periodic acid-Schiff and Masson’s Trichrome staining showed that intranasal HDM challenge induced severe mucus production and collagen deposition accompanied by inflammation in bronchial regions in the high expression MIF humanised mice. Importantly, human MSCs significantly reduced mucus production and collagen deposition.