当前位置： SCI文献检索 > WORLD JOURNAL OF GASTROENTEROLOGY期刊下所有文献 > 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?

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 × 10(6) 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 dUDP-biotin 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). CONCLUSION:Our results demonstrate that intravenous treatment is a superior method for reducing colon inflammation compared with intraperitoneal therapy.

journal_name

World J Gastroenterol

journal_title

World journal of gastroenterology

authors

Gonçalves Fda C,Schneider N,Pinto FO,Meyer FS,Visioli F,Pfaffenseller B,Lopez PL,Passos EP,Cirne-Lima EO,Meurer L,Paz AH

doi

10.3748/wjg.v20.i48.18228

subject

Has Abstract

pub_date

2014-12-28 00:00:00

pages

18228-39

issue

eissn

1007-9327

issn

2219-2840

journal_volume

pub_type

杂志文章

在线工具

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