Repositório Digital

A- A A+

Intravenous vs intraperitoneal mesenchymal stem cells administration : what is the best route for treating experimental colitis?

.

Intravenous vs intraperitoneal mesenchymal stem cells administration : what is the best route for treating experimental colitis?

Mostrar registro completo

Estatísticas

Título Intravenous vs intraperitoneal mesenchymal stem cells administration : what is the best route for treating experimental colitis?
Autor Gonçalves, Fabiany da Costa
Schneider, Natália
Pinto, Fernanda Otesbelgue
Meyer, Fabiola Schons
Visioli, Fernanda
Pfaffenseller, Bianca
Lopes, Patrícia Luciana da Costa
Passos, Eduardo Pandolfi
Cirne Lima, Elizabeth Obino
Meurer, Luíse
Paz, Ana Helena da Rosa
Abstract AIM: To investigate the therapeutic effects of mesenchymal stem cells (MSCs) transplanted intraperitoneally and intravenously in a murine model of colitis. METHODS: MSCs were isolated from C57BL/6 mouse adipose tissue. MSC cultures were analyzed according to morphology, cellular differentiation potential, and surface molecular markers. Experimental acute colitis was induced in C57BL/6 mice by oral administration of 2% dextran sulfate sodium (DSS) in drinking water ad libitum from days 0 to 7. Colitis mice were treated with 1 × 106 MSCs via intraperitoneal or intravenous injection on days 2 and 5. The disease activity index was determined daily based on the following parameters: weight loss, stool consistency and presence of blood in the feces and anus. To compare morphological and functional differences in tissue regeneration between different MSC injection modalities, mice were euthanized on day 8, and their colons were examined for length, weight, and histopathological changes. Inflammatory responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 kit. Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated dUDPbiotin nick end labeling assay. RESULTS: Intravenous infusion of MSCs was more effective than intraperitoneal treatment (P < 0.001) in reducing the clinical and histopathologic severity of colitis, which includes weight loss, diarrhea and inflammation. An histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory cells. This therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)]; and by the up-regulation of anti-inflammatory cytokines (IL-10 and IL-4). Intravenous transplantation also induced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs, which did not occur with intraperitoneal transplantation (P = 0.006). An increase in apoptotic T cells was observed after intravenous, but not intraperitoneal, MSC infusion, suggesting that MSCs can induce apoptosis in resistant T cells in colonic inflammation (P = 0.027).
Contido em World journal of gastroenterology. Beijing. Vol. 20, no. 48 (Dec. 2014), p. 18228-18239
Assunto Células-tronco mesenquimais
Colite ulcerativa
Doenças inflamatórias intestinais
Injeções intravenosas
[en] Cell transplantation
[en] Dextran sulfate sodium
[en] Immunomodulation
[en] Inflammatory bowel disease
[en] Intravenous injection
[en] Mesenchymal stem cell
[en] Ulcerative colitis
Origem Estrangeiro
Tipo Artigo de periódico
URI http://hdl.handle.net/10183/115707
Arquivos Descrição Formato
000952068.pdf (1.439Mb) Texto completo (inglês) Adobe PDF Visualizar/abrir

Este item está licenciado na Creative Commons License

Este item aparece na(s) seguinte(s) coleção(ões)


Mostrar registro completo

Percorrer



  • O autor é titular dos direitos autorais dos documentos disponíveis neste repositório e é vedada, nos termos da lei, a comercialização de qualquer espécie sem sua autorização prévia.
    Projeto gráfico elaborado pelo Caixola - Clube de Criação Fabico/UFRGS Powered by DSpace software, Version 1.8.1.