Intranasal or intraperitoneal administration of human tubal mesenchymal stem cells reduces T lymphocytes-associated lung inflammation in cigarette-induced emphysema in mice (IRC10P.415)

Abstract

Objective: To study the effectiveness of human tubal Estromal Stem Cells (htESCs) therapy by intra-nasal or intra-peritoneal route in experimental cigarette smoke-induced emphysema in C57BL/6 mice. Design: To achieve that, C57BL/6 mice were exposed to cigarette smoke for 75 days (2 times / day) and received or not two doses of htMSCS either intraperitoneally or intranasally. Experiments were performed on day 76th. Materials and Methods: Briefly, brochoalveolar lavage fluid was obtained and either used to measure cytokine secretion or inflammatory infiltrate. Moreover, lung tissue was also submitted to imunohistochemistry for the transcription factors NF-AT and NF-kB and also IL-10. Results: Our results clearly show that htMSCs greatly reduced lung inflammation, with decreased cellular infiltrate of T CD4 and T CD8 lymphocytes, which was confirmed by reduced NF-AT staining in lung tissues. This was associated with reduced pro-inflammatory cytokine secretion, as TNF-a, IL-1b and IL-6, less mucus and collagen deposition, and interestingly, increased IL-10. Conclusion: Altogether, our data indicate that therapy with htMSCs for the treatment of emphysematous disease may be a promising clinical approach. Moreover, intranasal route is also effective, and must taken in consideration due to its lack of invasiveness.