Human mesenchymal stem cells and immunosuppressive drug interactions in allogeneic responses: an in vitro study using human cells.
OBJECTIVE
The use of mesenchymal stem cells (MSC), which display immunosuppressive activity, seems to be a promising therapeutic approach in solid organ transplantation. However, little is known about their interactions with immunosuppressive drugs. The objective of this study was to assess these interactions in allogeneic responses.


METHODS
We studied the effects on alloimmune responses in mixed lymphocyte reactions of MSC plus five agents-cyclosporine, tacrolimus, rapamycin, mycophenolate acid (MPA), and dexamethasone (DEX).


RESULTS
Human MSC isolated from bone marrow were characterized by their phenotype and their ability to differentiate into adipocytes or osteoblastes. MSC plus the agents inhibited allogeneic lymphocyte proliferation in a dose-dependent manner. Calcineurin inhibitors and rapamycin antagonized the inhibitory effect of MSC, whereas MPA promoted it and DXM did not modify it.


CONCLUSIONS
MPA seems to be the best immunosuppressant to associated with MSC for transplanted patients.
INSERM U 851 Lyon, Université Lyon1, Villeurbanne, France. fanny.buron@free.fr
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F
Buron
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Perrin
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Malcus
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Héquet
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Thaunat
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Kholopp-Sarda
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Moulin
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Morelon
D017667:Adipocytes / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000276:immunology*; D009173:Mycophenolic Acid / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000276:immunology; D020123:Sirolimus / Q000494:pharmacology; D014184:Transplantation, Homologous / Q000276:immunology*
D015703:Antigens, CD; D007166:Immunosuppressive Agents; D003907:Dexamethasone; D016572:Cyclosporine; D009173:Mycophenolic Acid; D020123:Sirolimus