Both intranasal and intraperitoneal administration of human tubal mesenchymal stem cells (htMSC) ameliorates experimental COPD model

Chronic Obstructive Pulmonary Disease (COPD) is poorly managed with currently available therapies. Accordingly, the use of mesenchymal stem cells (MSCs) is an innovative and accessible treatment of pulmonary chronic diseases. These cells have an important therapeutic potential, being immune suppressive, anti-fibrogenic, promoters of tissue progenitor cells, anti-apoptotic. Thus, we investigated the effect of human tubal-derived MSCs (htMSCs) in the treatment of cigarette smoke-induced pulmonary inflammation in mice. To induce COPD C57Bl/6 mice were submitted to cigarette smoke for 75 days (2 times/day). Next, animals were treated with htMSCs by intraperitoneal (COPD+htMSC(ip) group) or intranasal route (COPD+htMSC(in) group) 7 and 15 days before the experiment on day 76 th , when mice were euthanized for morphologic and functional analysis of the lungs. Bronchoalveolar lavage (BAL) analysis showed that COPD+htMSC(ip) and COPD+LLL+htMSC(in) groups had a significant decrease in total cells, neutrophils and macrophages when compared to COPD group. The number of lymphocytes was more reduced in COPD+htMSC(ip) than COPD+htMSC(in) group. Both routes reduce mucous secretion, collagen deposition and alveolar enlargement, associated with reduced IL-1beta, IL-6, KC and TNF-a in BAL. More interestingly, lung expression of NF-KB and NFAT were both reduced in the experimental groups. However, the lung expression of IL-10 is increased only in COPD+htMSC(in) group. These results demonstrate that both htSMSC routes have anti-inflammatory effect on COPD, and thus may be considered as possible therapeutic approaches. Financial Support: UNINOVE, FAPESP, CNPq.