Mesenchymal stromal cells modulate gut inflammation in experimental colitis

Author(s)

de Aguiar, Cristhiane Favero ^[1] ; Castoldi, Angela ^[1] ; Andrade-Oliveira, Vinicius ^[1] ; Ignacio, Aline ^[1] ; da Cunha, Flavia Franco ^[2] ; Ferreira Felizardo, Raphael Jose ^[2] ; Bassi, Enio Jose ^[3] ; Saraiva Camara, Niels Olsen ^{[2, 1, 4, 5]} ; de Almeida, Danilo Candido ^{[2, 1, 4]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Nephrol Div, Dept Med, Sao Paulo - Brazil

^[3] Univ Fed Alagoas, Inst Biol Sci & Hlth, Alagoas - Brazil

^[4] Av Prof Lineu Prestes 1730 Lab 238 Cidade Univ, BR-05508000 Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Sch Med, LIM 16, Sao Paulo - Brazil

• Document type: Journal article
• Source: INFLAMMOPHARMACOLOGY; v. 26, n. 1, p. 251-260, FEB 2018.
• Web of Science Citations: 4

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-gamma, TNF-alpha, 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. (AU)

• FAPESP's process: 13/25327-2 - Role of inflammatory microenvironment in activation and biology of mesenchymal stem cells
• Grantee: Danilo Candido de Almeida
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/16794-3 - Influence of gut microbiota on NKT cells profile in an experimental model of colitis
• Grantee: Cristhiane Favero de Aguiar
• Support Opportunities: Scholarships in Brazil - Doctorate