Effect of mesenchymal stem cells on inhibiting airway remodeling and airway inflammation in chronic asthma

Abstract

Previous studies proved that bone marrow-derived mesenchymal stem cells (BMSCs) could improve a variety of immune-mediated disease by its immunomodulatory properties. In this study, we investigated the effect on airway remodeling and airway inflammation by administrating BMSCs in chronic asthmatic mice. Forty-eight female BALB/c mice were randomly distributed into PBS group, BMSCs treatment group, BMSCs control group, and asthmatic group. The levels of cytokine and immunoglobulin in serum and bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay. The number of CD4(+) CD25(+) regulatory T cells and morphometric analysis was determined by flow cytometry, hematoxylin-eosin, immunofluorescence staining, periodic-acid Schiff, and masson staining, respectively. We found that airway remodeling and airway inflammation were evident in asthmatic mice. Moreover, low level of IL-12 and high levels of IL-13, IL-4, OVA-specific IgG1, IgE, and IgG2a and the fewer number of CD4(+) CD25(+) regulatory T cells were present in asthmatic group. However, transplantation of BMSCs significantly decreased airway inflammation and airway remodeling and level of IL-4, OVA-specific IgE, and OVA-specific IgG1, but elevated level of IL-12 and the number of CD4 + CD25 + regulatory T cells in asthma (P < 0.05). However, BMSCs did not contribute to lung regeneration and had no significant effect on levels of IL-10, IFN-Y, and IL-13. In our study, BMSCs engraftment prohibited airway inflammation and airway remodeling in chronic asthmatic group. The beneficial effect of BMSCs might involved the modulation imbalance cytokine toward a new balance Th1-Th2 profiles and up-regulation of protective CD4 + CD25 + regulatory T cells in asthma, but not contribution to lung regeneration.

Stem cells in animal asthma models: a systematic review

“…No significant effect was seen in 2 studies, including the Lathrop et al study [9,13]. MSC treatment led to a significant decrease in BAL IL-13 levels in 3 studies [9,15,17] (P < 0.001 to P < 0.05), including with treatment after allergen challenge [15], whereas BAL IL-13 levels were already low in controls in 1 study [25] and there was no significant change in 5 studies [12,13,20,23,24]. One short-term study that reported on IL-9 levels in BAL found a reduction with MSC treatment (P < 0.05) [26].…”

“…MSC administration occurred before allergen challenge most commonly but also occurred before sensitization [11,17,20,21] or after allergen challenge [12,14,15,18,22] in other studies. MSCs were administered intravenously in all but 3 studies [11,23,24] in which they were administered intratracheally.…”

“…BAL interleukin (IL)-4 levels were assessed in 11 studies [9,12,13,17e21,23,24,26] and were found to be significantly decreased with MSC treatment in 8 studies (P < 0.05), including with treatment before sensitization [17,20,21], with treatment before allergen challenge [9,17,19,23,26] and with treatment after allergen challenge [18]. No significant effect was seen in the Lathrop [13] study, the Mariñas-Pardo [12] study, one of the Ge studies [24] and in one group of the Sun study.…”

Human Mesenchymal Stem Cells Resolve Airway Inflammation, Hyperreactivity, and Histopathology in a Mouse Model of Occupational Asthma

“…Recent reports have demonstrated the anti-inflammatory potential of MSCs in several murine asthma models induced by high-molecular-weight allergens (ovalbumin, ragweed, and aspergillus hyphal extract) [11,13,[22][23][24][25][26][27][28] and in a low-molecular-weight, toluene diisocyanate (TDI)-induced asthma model [14]. However, in most of these models, the MSCs were administered preventively, that is, during the immunization phase or concomitantly with the induction of asthma.…”

Treatment of silicosis with hepatocyte growth factor-modified autologous bone marrow stromal cells: a non-randomized study with follow-up

“…Increased IgG levels were also reported by Sauni et al, 2012. In a chronic asthmatic mouse model, it was found that administering MSCs could decrease airway inflammation and airway remodeling by elevating IL-12 concentrations and the number of regulatory T cells, resulting in the re-balance of the local immune system (Ge et al, 2013).…”