Immunosuppression by placental indoleamine 2,3-dioxygenase: a role for mesenchymal stem cells.
OBJECTIVE
Mesenchymal stem cells (MSC) can be isolated from human placenta and have the potential to contribute to the immunosuppressive properties of placental tissue. The objectives of this study were to investigate the phenotype and differentiation characteristics of MSC derived from human placenta and evaluate the role of the tryptophan degrading enzyme, indoleamine 2,3 dioxygenase (IDO), in mediating their immunosuppressive affect.


METHODS
MSC obtained from placental tissue (pMSC) were characterised using flow cytometry and tested for multipotency by determining differentiation into all mesenchymal lineages. The immunosuppressive properties of pMSC were tested in allogeneic mixed lymphocyte reactions and IDO expression and activity were measured by semi-quantitative real-time PCR and HPLC respectively.


RESULTS
Multipotent stem cells were isolated from placenta and displayed chondrogenic, osteogenic and limited adipogenic differentiation. Cell surface antigen expression of pMSC was similar to bone marrow MSC (bMSC) with lack of the haematopoietic and common leukocyte markers (CD34, CD45), and expression of adhesion (CD29, CD166, CD44) and stem cell (CD 90, CD105, CD73) markers. Placental MSC were suppressive of allogeneic T-cell proliferation, an effect which was intensified following IDO induction by IFN-gamma. Replenishment of tryptophan or treatment with the IDO-blocker, 1-methyl-tryptophan (1-MT), attenuated the immunosuppressive action of pMSC.


CONCLUSIONS
These results suggest that placental tissue contains MSC, which are phenotypically and functionally similar to bMSC, and that IDO is a key mediator of their immunosuppressive effect. Further investigation is needed to determine if pMSC function effects pregnancy outcome.
Jones
B J
BJ
Biotherapy Program, Mater Medical Research Institute, South Brisbane, QLD 4101, Australia.
Brooke
G
G
Atkinson
K
K
McTaggart
S J
SJ
D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000502:physiology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D010920:Placenta / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007519:Isoantigens; D012333:RNA, Messenger; D007371:Interferon-gamma