Adipose-tissue-derived and Wharton's jelly-derived mesenchymal stromal cells suppress lymphocyte responses by secreting leukemia inhibitory factor.
Mesenchymal stromal cells (MSCs) possess immunomodulatory functions and have been proposed as a tool for managing or preventing graft-versus-host disease. Recently, adipose tissue (AT) and Wharton's jelly (WJ) have been reported as potential alternative MSC sources to bone marrow (BM). In this study, we investigated the capacity of MSCs derived from AT and WJ to modulate lymphocyte proliferation as well as their impact on regulatory T-cells. We also evaluated MSC expression of leukemia inhibitory factor and the role of this molecule in the mechanism of MSC-mediated inhibition. We demonstrated that WJ- and AT-MSCs induced a dose-dependent inhibition of T-cell proliferation regardless of the stimuli used to activate T-cells. WJ- and AT-MSCs were more potent than BM-MSCs in suppressing lymphocyte responses, and they mediated this effect by secreting high levels of leukemia inhibitory factor. We also observed that WJ- and AT-MSCs maintained and promoted the expansion of regulatory T-cells independently of the MSC/T-cell ratio. Because human WJ and AT contain MSCs with potent immunomodulatory capacities, they could represent an alternative to BM. Using WJ- and AT-MSCs in clinical therapies, such as the prevention and/or reduction of graft-versus-host disease and in the treatment of autoimmune diseases, is particularly promising. Further characterization of MSC physiological functions will increase the safety and efficacy of their use in clinical settings.
Najar
Mehdi
M
Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. mnajar@ulb.ac.be
Raicevic
Gordana
G
Boufker
Hicham Id
HI
Fayyad-Kazan
Hussein
H
De Bruyn
Cécile
C
Meuleman
Nathalie
N
Bron
Dominique
D
Toungouz
Michel
M
Lagneaux
Laurence
L
D000273:Adipose Tissue / Q000166:cytology*; D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007165:Immunosuppression Therapy; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility / Q000187:drug effects; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014470:Umbilical Cord / Q000166:cytology*; D055815:Young Adult
D057134:Antibodies, Neutralizing; D053605:Leukemia Inhibitory Factor; D008934:Mitogens; D012333:RNA, Messenger