TY - JOUR
T1 - The immunosuppressive signature of menstrual blood mesenchymal stem cells entails opposite effects on experimental arthritis and graft versus host diseases
AU - Luz-Crawford, Patricia
AU - Torres, Maria J.
AU - Noël, Daniele
AU - Fernandez, Ainoa
AU - Toupet, Karine
AU - Alcayaga-Miranda, Francisca
AU - Tejedor, Gautier
AU - Jorgensen, Christian
AU - Illanes, Sebastian E.
AU - Figueroa, Fernando E.
AU - Djouad, Farida
AU - Khoury, Maroun
N1 - Publisher Copyright:
© 2015 AlphaMed Press.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Recently, a noninvasive and highly proliferative stem cell population from menstrual blood called MenSCs has been identified. Despite their use in clinical studies, their immunomodulatory properties have not yet been investigated. In this context, we studied the immunosuppressive properties of MenSCs in comparison with the well-characterized bone marrow derived-MSCs (BM-MSCs). Using an in vitro proliferation assays, we showed that MenSCs displayed a lower suppressive effect on peripheral blood mononuclear cells and in particular on the proinflammatory CD4+IFN-γ+ and CD8+IFNγ+ cells than BM-MSCs. Moreover, compared to BM-MSCs, MenSCs activated with IFN-γ and IL-1β produced lower amounts of immunosuppressive factors such as IDO, PDL-1, PGE2, and Activin A and exhibited a substantial lower expression level of IFN-γ receptor subunits. In the collagen induced arthritis model, while BM-MSCs administration resulted in a potent therapeutic effect associated with a significant decrease of proinflammatory T cell frequency in the lymph nodes, MenSCs injection did not. In contrast, in the xeno-GVHD model, only MenSCs administration significantly increased the survival of mice. This beneficial effect mediated by MenSCs was associated with a higher capacity to migrate into the intestine and liver and not to their anti-inflammatory capacities. All together our results demonstrate for the first time that the therapeutic potential of MSC in the experimental xeno-GVHD model is independent of their immunosuppressive properties. These findings should be taken into consideration for the development of safe and effective cell therapies.
AB - Recently, a noninvasive and highly proliferative stem cell population from menstrual blood called MenSCs has been identified. Despite their use in clinical studies, their immunomodulatory properties have not yet been investigated. In this context, we studied the immunosuppressive properties of MenSCs in comparison with the well-characterized bone marrow derived-MSCs (BM-MSCs). Using an in vitro proliferation assays, we showed that MenSCs displayed a lower suppressive effect on peripheral blood mononuclear cells and in particular on the proinflammatory CD4+IFN-γ+ and CD8+IFNγ+ cells than BM-MSCs. Moreover, compared to BM-MSCs, MenSCs activated with IFN-γ and IL-1β produced lower amounts of immunosuppressive factors such as IDO, PDL-1, PGE2, and Activin A and exhibited a substantial lower expression level of IFN-γ receptor subunits. In the collagen induced arthritis model, while BM-MSCs administration resulted in a potent therapeutic effect associated with a significant decrease of proinflammatory T cell frequency in the lymph nodes, MenSCs injection did not. In contrast, in the xeno-GVHD model, only MenSCs administration significantly increased the survival of mice. This beneficial effect mediated by MenSCs was associated with a higher capacity to migrate into the intestine and liver and not to their anti-inflammatory capacities. All together our results demonstrate for the first time that the therapeutic potential of MSC in the experimental xeno-GVHD model is independent of their immunosuppressive properties. These findings should be taken into consideration for the development of safe and effective cell therapies.
KW - CIA
KW - GVHD
KW - Immunosuppression
KW - Menstrual-blood derived MSCs
UR - http://www.scopus.com/inward/record.url?scp=84958260900&partnerID=8YFLogxK
U2 - 10.1002/stem.2244
DO - 10.1002/stem.2244
M3 - Article
C2 - 26528946
AN - SCOPUS:84958260900
SN - 1066-5099
VL - 34
SP - 456
EP - 469
JO - Stem Cells
JF - Stem Cells
IS - 2
ER -