Interleukin-10-Overexpressing Mesenchymal Stromal Cells Induce a Series of Regulatory Effects in the Inflammatory System and Promote the Survival of Endotoxin-Induced Acute Lung Injury in Mice Model

• Published in: DNA and cell biology Vol. 37; no. 1; p. 53
• Main Authors: Wang, Chenfei, Lv, Dan, Zhang, Xiaobin, Ni, Zhu-Ang, Sun, Xiaofan, Zhu, Changqing
• Format: Journal Article
• Language: English
• Published: United States 01.01.2018
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - metabolism; Animals; Disease Models, Animal; Endotoxins - pharmacology; Inflammation - chemically induced; Inflammation - metabolism; Interleukin-10 - metabolism; Lipopolysaccharides - pharmacology; Lung - drug effects; Lung - metabolism; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred C57BL; acute lung injury; interleukin 10; mesenchymal stromal cell
• DOI: 10.1089/dna.2017.3735

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening inflammatory conditions with no effective pharmacological treatment. Previous studies suggested that mesenchymal stromal/stem cell (MSC) infusion resulted in better survival in mouse ALI models and presented low toxicity in human subjects. Therefore, in this study, we investigated the possibility of treating a murine model of ALI using MSCs with constant interleukin-10 overexpression (IL-10-MSC) by retroviral infection. ALI in mice was induced by intratracheal lipopolysaccharides (LPS) instillation. After 96 h, 80% of mice receiving IL-10-MSCs survived, whereas the survival rate of the mice receiving other treatments was only 20-50%. Mice receiving IL-10-MSCs also demonstrated significantly less weight loss (p < 0.01), and lower protein level and TNF concentration in the BAL (p < 0.01). Interestingly, IL-10-MSCs given to mice 3 and 1 day before ALI induction still conferred significant protection against ALI. While direct IL-10 transfusion resulted in an intensive, but transient peak in serum IL-10 level, IL-10-MSCs provided a milder, but more persistent increase in serum IL-10 level, together with significantly higher levels of IL-10-producing T cells and B cells, both in the spleen and in the lung. IL-10-MSCs given 3 days before LPS challenge resulted in higher pulmonary infiltration of IL-10-producing T cells and B cells in mice. On average, mice that survived the LPS challenge for 96 h presented higher pulmonary infiltration of IL-10-producing T cells and B cells than mice that deceased within the experimental period. Together, these results demonstrated that IL-10-MSCs offered superior protection against LPS-induced ALI when given before or at the time of ALI induction, and significantly increased the frequencies of IL-10-expressing T cells and B cells. IL-10-MSCs may thus represent a promising new treatment option in ALI/ARDS.