Tags

Type your tag names separated by a space and hit enter

Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis.
Gut 2009; 58(7):929-39Gut

Abstract

BACKGROUND AND AIMS

Inflammatory bowel diseases (IBDs) are associated with uncontrolled innate and adaptive immunity against normal constituents, including commensal bacteria and microbial products. Mesenchymal stem cells (MSCs) suppress effector T cell responses and have beneficial effects in various immune disorders. This work investigates the therapeutic effects of human adipose-derived MSCs (hASCs) in various models of IBD and sepsis.

METHODS

Acute and chronic colitis was induced in mice with dextran sulfate sodium. Sepsis was induced by caecal ligation and puncture or by endotoxin injection. Colitic and septic mice were treated intraperitoneally with hASCs or murine ASCs, and diverse disease clinical signs and mortality were determined. The levels of various inflammatory cytokines and chemokines, T helper 1(Th1)-type response and generation of regulatory T cells (Treg) were determined in affected organs.

RESULTS

Systemic infusion of ASCs significantly ameliorated the clinical and histopathological severity of colitis, abrogating weight loss, diarrhoea and inflammation, and increasing survival. The therapeutic effect was associated with downregulation of the Th1-driven inflammatory responses. ASCs decreased a wide panel of inflammatory cytokines and chemokines and increased interleukin 10 (IL10), acting on macrophages. hASCs also impaired Th1 cell activation in both colonic mucosa and draining lymph nodes. The induction of IL10-secreting Treg was partially involved in the therapeutic effect of hASCs. Moreover, ASCs protected from severe sepsis by reducing the infiltration of inflammatory cells in various target organs and by downregulating the production of various inflammatory mediators.

CONCLUSIONS

hASCs emerge as key regulators of immune/inflammatory responses in vivo and as attractive candidates for cell-based treatments for IBD and sepsis.

Authors+Show Affiliations

School of Medicine, University of Seville, Seville, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19136511

Citation

Gonzalez-Rey, E, et al. "Human Adult Stem Cells Derived From Adipose Tissue Protect Against Experimental Colitis and Sepsis." Gut, vol. 58, no. 7, 2009, pp. 929-39.
Gonzalez-Rey E, Anderson P, González MA, et al. Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut. 2009;58(7):929-39.
Gonzalez-Rey, E., Anderson, P., González, M. A., Rico, L., Büscher, D., & Delgado, M. (2009). Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut, 58(7), pp. 929-39. doi:10.1136/gut.2008.168534.
Gonzalez-Rey E, et al. Human Adult Stem Cells Derived From Adipose Tissue Protect Against Experimental Colitis and Sepsis. Gut. 2009;58(7):929-39. PubMed PMID: 19136511.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. AU - Gonzalez-Rey,E, AU - Anderson,P, AU - González,M A, AU - Rico,L, AU - Büscher,D, AU - Delgado,M, Y1 - 2009/01/09/ PY - 2009/1/13/entrez PY - 2009/1/13/pubmed PY - 2009/7/11/medline SP - 929 EP - 39 JF - Gut JO - Gut VL - 58 IS - 7 N2 - BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) are associated with uncontrolled innate and adaptive immunity against normal constituents, including commensal bacteria and microbial products. Mesenchymal stem cells (MSCs) suppress effector T cell responses and have beneficial effects in various immune disorders. This work investigates the therapeutic effects of human adipose-derived MSCs (hASCs) in various models of IBD and sepsis. METHODS: Acute and chronic colitis was induced in mice with dextran sulfate sodium. Sepsis was induced by caecal ligation and puncture or by endotoxin injection. Colitic and septic mice were treated intraperitoneally with hASCs or murine ASCs, and diverse disease clinical signs and mortality were determined. The levels of various inflammatory cytokines and chemokines, T helper 1(Th1)-type response and generation of regulatory T cells (Treg) were determined in affected organs. RESULTS: Systemic infusion of ASCs significantly ameliorated the clinical and histopathological severity of colitis, abrogating weight loss, diarrhoea and inflammation, and increasing survival. The therapeutic effect was associated with downregulation of the Th1-driven inflammatory responses. ASCs decreased a wide panel of inflammatory cytokines and chemokines and increased interleukin 10 (IL10), acting on macrophages. hASCs also impaired Th1 cell activation in both colonic mucosa and draining lymph nodes. The induction of IL10-secreting Treg was partially involved in the therapeutic effect of hASCs. Moreover, ASCs protected from severe sepsis by reducing the infiltration of inflammatory cells in various target organs and by downregulating the production of various inflammatory mediators. CONCLUSIONS: hASCs emerge as key regulators of immune/inflammatory responses in vivo and as attractive candidates for cell-based treatments for IBD and sepsis. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/19136511/Human_adult_stem_cells_derived_from_adipose_tissue_protect_against_experimental_colitis_and_sepsis_ L2 - http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=19136511 DB - PRIME DP - Unbound Medicine ER -