Inflammopharmacology. 2017 Oct 23. doi: 10.1007/s10787-017-0404-6. [Epub ahead of print]

Mesenchymal stromal cells modulate gut inflammation in experimental colitis.

de Aguiar CF¹, Castoldi A¹, Andrade-Oliveira V¹, Ignacio A¹, da Cunha FF², Felizardo RJF², Bassi ÊJ³, Câmara NOS^4,5,6,7, de Almeida DC^8,9,10.

Abstract

Inflammatory bowel diseases (IBDs) affect millions of people worldwide and their frequencies in developed countries have increased since the twentieth century. In this context, there is an intensive search for therapies that modulate inflammation and provide tissue regeneration in IBDs. Recently, the immunomodulatory activity of adipose tissue-derived mesenchymal stromal cells (ADMSCs) has been demonstrated to play an important role on several immune cells in different conditions of inflammatory and autoimmune diseases. In this study, we explored the immunomodulatory potential of ADMSC in a classical model of DSS-induced colitis. First, we found that treatment of mice with ADMSC ameliorated the severity of DSS-induced colitis, reducing colitis pathological score and preventing colon shortening. Moreover, a prominent reduction of pro-inflammatory cytokines levels (i.e., IFN-γ, TNF-α, IL-6 and MCP-1) was observed in the colon of animals treated with ADMSC. We also observed a significant reduction in the frequencies of macrophages (F4/80⁺CD11b⁺) and dendritic cells (CD11c⁺CD103⁺) in the intestinal lamina propria of ADMSC-treated mice. Finally, we detected the up-regulation of immunoregulatory-associated molecules in intestine of mice treated with ADMSCs (i.e., elevated arginase-1 and IL-10). Thus, this present study demonstrated that ADMSC modulates the overall gut inflammation (cell activation and recruitment) in experimental colitis, providing support to the further development of new strategies in the treatment of intestinal diseases.