Selected Stro-1-enriched bone marrow stromal cells display a major suppressive effect on lymphocyte proliferation.
Mesenchymal stem cells (MSCs) have an immunosuppressive effect and can inhibit the proliferation of alloreactive T cells in vitro and in vivo. Cotransplantation of MSCs and hematopoietic stem cells (HSCs) from HLA-identical siblings has been shown to reduce the incidence of acute graft-vs.-host disease. MSCs are heterogeneous and data on the inhibitory effects of different MSC subsets are lacking. The antigen Stro1 is a marker for a pure primitive MSC subset. We investigated whether Stro-1-enriched induce a more significant suppressive effect on lymphocytes in a mixed lymphocyte reaction (MLR), and whether this action is related to a specific gene expression profile in Stro-1-enriched compared to other MSCs. We demonstrated that the Stro-1-enriched population elicits a significantly more profound dose-dependent inhibition of lymphocyte proliferation in a MLR than MSCs. One thousand expanded Stro-1-enriched induced an inhibitory effect comparable to that of 10 times as many MSCs. Inhibition by Stro-1-enriched was more significant in contact-dependent cultures than in noncontact-dependant cultures at higher ratio. The Stro-1-enriched inhibitory effect in both culture types was linked to increased gene expression for soluble inhibitory factors such as interleukin-8 (IL-8), leukemia inhibitory factor (LIF), indoleamine oxidase (IDO), human leukocyte antigen-G (HLA-G), and vascular cell adhesion molecule (VCAM1). However, tumor growth factor-beta1 (TGF-beta) and IL-10 were only up-regulated in contact-dependant cultures. These results may support using a purified Stro-1-enriched population to augment the suppressive effect in allogeneic transplantation.
Nasef
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A
EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle (LTCRA), Faculté de médecine Saint Antoine, Université Paris VI, Paris, France.
Zhang
Y Z
YZ
Mazurier
C
C
Bouchet
S
S
Bensidhoum
M
M
Francois
S
S
Gorin
N C
NC
Lopez
M
M
Thierry
D
D
Fouillard
L
L
Chapel
A
A
D000954:Antigens, Surface / Q000235:genetics / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008875:Middle Aged; D017154:Stromal Cells
D000954:Antigens, Surface; C525591:STRO-1 antigen, human