Adipose-derived mesenchymal stromal cells induce immunomodulatory macrophages which protect from experimental colitis and sepsis.
Gut
; 62(8): 1131-41, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-22637701
ABSTRACT
OBJECTIVE:
To investigate the effect of adipose-derived mesenchymal stromal cells (ASCs) on the activation state of macrophages (MΦ) in vitro, and the potential therapeutic effect of these cells in experimental colitis and sepsis.DESIGN:
Murine bone marrow-derived macrophages were cultured with ASCs or with ASC conditioned media (ASC-MΦ) and characterised for the expression of several regulatory macrophage markers, including enzymes and cytokines, and for their immunomodulatory capacity in vitro. The therapeutic effect was investigated of ASC-MΦ in two models of experimental inflammatory colitis induced by trinitrobenzene sulphonic acid and dextran sodium sulphate, and in polymicrobial sepsis induced by caecal ligation and puncture.RESULTS:
ASC-MΦ showed a phenotype that clearly differed from the classically activated macrophages or the alternatively activated macrophages induced by interleukin (IL)-4, characterised by high arginase activity, increased production of IL-10 upon restimulation and potent immunosuppressive activity on T cells and macrophages. Activation of cyclo-oxygenase-2 on ASCs seems to be critically involved in inducing this phenotype. Systemic infusion of ASC-MΦ inhibited colitis in mice, reducing mortality and weight loss while lowering the colonic and systemic levels of inflammatory cytokines. Importantly, therapeutic injection of ASC-MΦ in established chronic colitis alleviated its progression and avoided disease recurrence. Moreover, ASC-MΦ protected from severe sepsis by reducing the infiltration of inflammatory cells into various organs and by downregulating the production of several inflammatory mediators, where ASC-MΦ-derived IL-10 played a critical role.CONCLUSION:
ASCs induce a distinct regulatory activation state of macrophages which possess potent immunomodulatory ability and therapeutic potential in inflammatory bowel diseases and sepsis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo
/
Colite
/
Sepse
/
Células-Tronco Mesenquimais
/
Macrófagos
Tipo de estudo:
Evaluation_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article