RESEARCH - Human adipose-derived mesenchymal stem cells reduce inflammatory and T-cell responses and induce regulatory T cells in vitro in RA

[Guest guest]

Ann Rheum Dis. Published Online First: 5 January 2009.

doi:10.1136/ard.2008.101881

--------------------------------------------------------------------------------

Extended Report

Human adipose-derived mesenchymal stem cells reduce inflammatory and

T-cell responses and induce regulatory T cells in vitro in rheumatoid

arthritis

Elena -Rey 1, A 2, Nieves Varela 3, Francisco

O'Valle 4, Pedro -Cortes 5, Rico 6, Dirk Büscher 6 and

Delgado 3*

1 School of Medicine, Seville University, Seville, Spain

2 Fundación Centro Nacional de Investigaciones Cardiovasculares

III (CNIC), Madrid, Spain

3 Instituto de Parasitologia y Biomedicina, CSIC, Granada, Spain

4 School of Medicine, University of Granada, Spain

5 San Cecilio University Hospital, Spain

6 Cellerix, SA, Madrid, Spain

Abstract

Objectives: Adult mesenchymal stem cells were recently found to

suppress effector T-cell and inflammatory responses and have emerged

as attractive therapeutic candidates for immune disorders. In

rheumatoid arthritis (RA), a loss in the immunological self-tolerance

causes the activation of autorreactive T cells against joint

components and subsequent chronic inflammation. The aim of this study

is to characterize the immunosuppresive activity of human

adipose-derived mesenchymal stem cells (hASCs) on collagen-reactive T

cells from RA patients.

Methods: We investigated the effects of hASCs on collagen-reactive RA

human T-cell proliferation and cytokine production, as well as on the

production of inflammatory mediators by monocytes and fibroblast-like

synoviocytes from RA patients.

Results: hASCs suppressed antigen-specific response of T cells from RA

patients. hASCs inhibited the proliferative response and the

production of inflammatory cytokines by collagen-activated CD4 and CD8

T cells. In contrast, the number of IL-10-producing T cells and

monocytes significantly augmented upon hASC-treatment. The suppressive

activity of hASCs was both cell-to-cell contact-dependent and

-independent. hASCs also stimulated the generation of FoxP3-expressing

CD4+CD25+ regulatory T cells with capacity to suppress

collagen-specific T-cell responses. Finally, hASCs donwregulated the

inflammatory response and the production of matrix-degrading enzymes

by synovial cells isolated from RA patients.

Conclusions: Our work identifies to hASCs as key regulators of immune

tolerance with capacity to suppress T-cell and inflammatory responses

to induce the generation/activation of antigen-specific regulatory T

cells.

http://ard.bmj.com/cgi/content/abstract/ard.2008.101121v1?papetoc

Not an MD