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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis

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Author(s):
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Freitas Alves, V. B. [1, 2] ; Coutinho de Sousa, B. [1] ; Thais Costa Fonseca, M. [1, 3] ; Ogata, H. [1] ; Caliari-Oliveira, C. [3, 4] ; Navarro Ueda Yaochite, J. [3, 5] ; Rodrigues Junior, V. [1] ; Lazo Chica, J. E. [1] ; Santana da Silva, J. [2, 3] ; Ribeiro Malmegrim, K. C. [2] ; Pernomian, L. [2] ; Ribeiro Cardoso, C. [2]
Total Authors: 12
Affiliation:
[1] Univ Fed Triangulo Mineiro, Inst Ciencias Biol & Nat, Uberaba, MG - Brazil
[2] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Dept Bioquim & Imunol, Fac Med Ribeirao Preto, Ribeirao Preto, SP - Brazil
[4] SUPERA Parque Inovacao & Tecnol Ribeirao Preto, In Situ Terapia Celular, Ribeirao Preto, SP - Brazil
[5] Univ Fed Ceara, Dept Anal Clin & Toxicol, Fac Farm, Odontol & Enfermagem, Fortaleza, Ceara - Brazil
Total Affiliations: 5
Document type: Journal article
Source: CLINICAL AND EXPERIMENTAL IMMUNOLOGY; v. 196, n. 2, p. 139-154, MAY 2019.
Web of Science Citations: 0
Abstract

Current therapies for inflammatory bowel diseases (IBD) are aimed at controlling the exacerbated response in the gut, but no treatment is fully effective for many refractory patients. Mesenchymal stromal cells (MSC) are multi-potent cells with regulatory immunosuppressive activity that may control inflammatory diseases. In this study, we investigated the short- and especially the long-term protective effects of MSC on experimental colitis. We show that MSC elicited protection to acute intestinal inflammation with gain of weight, improvement in the clinical disease score and expressive reduction in the mortality rate of treated mice. MSC changed the population of neutrophils, eosinophils and augmented the frequency of CD4 T lymphocytes in the gut-draining lymph nodes, together with reduced accumulation of these cells in the colon intraepithelial compartment. Interestingly, there were increased levels of programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor family-related receptor (GITR) in the spleen regulatory T cells of mice that received MSC treatment, which also presented a reversal in the pattern of immune response in the gut, with diminished inflammatory, T helper type 1 (Th1) and Th17 profile, in contrast to augmented Th2 responses. Most strikingly, this balanced response elicited by a single administration of MSC during the acute colitis persisted long-term, with restored goblet cells, eosinophils and maintenance of elevated gut interleukin (IL)-4, besides increased CD4(+)CD25(+)PD-1(+) cells in the spleen and reduced Th17 response in mesenteric lymph nodes (MLN) of treated mice on day 60. Taken together, our findings provided a significant contribution to translational immunology by pointing human adipose tissue-derived MSC as a novel therapeutic approach with long-term beneficial regulatory effects in experimental colitis. (AU)

FAPESP's process: 10/20162-7 - The role of hypothalamus-pituitary-adrenal (HPA) axis and exogenous glucocorticoids in the modulation of immune response in inflammatory bowel disease
Grantee:Cristina Ribeiro de Barros Cardoso
Support type: Research Grants - Young Investigators Grants