Adipose-derived Mesenchymal Stem Cells in Emphysema: Comparison of Inflammatory Markers Changes in Response to Intratracheal and Systemic Delivery Method

Cytokines are the most important inflammatory mediators and are well-known as the main cause of emphysema. Adipose-derived stem cells (ADSCs) as a cell-based treatment strategy could play a pivotal role in lung regeneration through anti-inflammatory and paracrine properties. Accordingly, the aim of this study was to the comparison of inflammation markers' improvement in response to the intratracheal and systemic delivery method of adipose-derived mesenchymal stem cells in emphysema. Forty-eight rats were divided into five groups including Control, Elastase (25 IU/kg, Intratracheal, at day first and 10th), Elastase+PBS, Intratracheal cell therapy (1 ×107, at day 28th), and Systemic cell therapy groups (1 ×107, Jugular vein, at day 28th). After 3 weeks, the blood gas analysis (PO2, PCO2 and pH), fibrinogen level, and C-reactive protein (CRP) concentrations were measured in all groups. In addition, inflammatory genes expression, and concentration levels of pro and anti-inflammatory cytokines (IL-6, IL-17, TNF-α, and TGF-β,) were evaluated using Real-time PCR and Elisa kits, respectively. The statistical analysis of our data shows that local administration leads to more significant treatment efficacy with decreased inflammation parameters such as WBC count and pro-inflammatory cytokines in comparison with systemic treatment. Besides, these results were approved by more reduction of CRP and fibrinogen concentration levels in blood samples of intra-tracheal AMSCs-treated rats compare with the systemic group. Moreover, the improvement in histopathology indexes of the local administrated group was significantly better than the systemic group. Accordingly, the obtained results suggest local administration as the most efficacious route for mesenchymal stem cells delivery in patients with emphysema.