Effects of human mesenchymal stem cells on airway inflammation in allergic asthma mice and the underlying mechanism of actions

Effects of human mesenchymal stem cells on airway inflammation in allergic asthma mice and the underlying mechanism of actions Ren N*, Chen, H, Chen Q, McGowan EW, An J, Lin Y. *Guangdong Online Hospital, Guangdong 2nd Provincial People’s Hospital, Guangzhou 510317, China Corresponding author: Yiguang Lin, School of Life Sciences, University of Technology Sydney, Broadway NSW 2007, Australia. email: yiguang.lin@uts.edu.au. 【Abstract】 Objectives To investigate the anti-inflammatory effects of human umbilical cord mesenchymal stem cells (hUC-MSCs) and mechanism of action in an ovalbumin (OVA) induced asthma mouse model. Methods Twenty-four BALB/c mice were randomly divided into four equal groups: normal control group, OVA-induced asthmatic model group, hUC-MSCs treated group (50 µl of hUC-MSCs was transplanted into the trachea of asthmatic mice ) and hUC-MSCs control group (50 µl of hUC-MSCs was transplanted into the trachea of control mice). Human umbilical cord mesenchymal stem cells from umbilical cord of healthy new born babies were used as the source of hUC-MSCs for this study. The asthmatic conditions of the airways and the lungs were assessed by examining: 1) histopathological changes of the airways and the lungs; 2) expression of cytokines IL-6 and TGF-β mRNA by real-time PCR; 3) total leukocytes and mast cell count in BALF and number of IL-17-expressing CD4+ cells (Th17 cells) in the lung tissue using flow cytometry. Results Typical histopathological changes of asthma were confirmed in the asthmatic model group. These changes included intensive inflammatory cell infiltration around the airways and patchy airway occlusion by hyperviscous mucus. The number of total leukocytes and mast cells in BALF were significantly increased in the asthmatic mice when compared with the control group (P<0.05). Mice in the asthmatic model group had significantly higher percentage of Th17 cells in lung tissues when compared with the control group (2.90% vs 0.76%, P<0.05). In contrast, in the asthmatic mice treated with hUC-MSCs, the inflammatory cell infiltration was significantly reduced compared with asthmatic mice, as observed by significantly lower leukocytes and mast cells in BALF (P<0.05) and significant reduction in the percentage of Th17 cells in the lung of OVA-challenged mice following hUC-MSCs treatment (percentage of Th17 cells: 0.24% vs 2.90%, P<0.05). The expression of mRNA for IL-6 and TGF-ß was significantly suppressed in the hUC-MSCs treatment group (0.23 vs 2.30 and 0.56 vs 6.60, both P