Donor-derived mesenchymal stem cells suppress alloreactivity of kidney transplant patients.
BACKGROUND
Human mesenchymal stem cells (MSC) have immunosuppressive capacities. Although their efficacy is currently studied in graft-versus-host disease, their effect on alloreactivity in solid organ transplant patients is unknown. In this study, the immunosuppressive effect of MSC on recipient anti-donor reactivity was examined before and after clinical kidney transplantation.


METHODS
Anti-donor reactivity was established in pretransplant and posttransplant mixed lymphocyte reactions (MLR) of 14 living-kidney donor-recipient pairs. MSC from donors and third-party controls were added to the MLR in a ratio of 1:5.


RESULTS
MSC were isolated from donor perirenal fat and showed multilineage differentiation potential and the capacity to inhibit lymphocyte proliferation. The immunosuppressive effect of MSC was dose dependent and mediated by cell-membrane contact and soluble factors, including interleukin-10 and indoleamine 2,3-dioxygenase.Donor-derived MSC significantly inhibited the recipient anti-donor reactivity before and 1 month after transplantation. This effect was independent of human leukocyte antigen background of MSC. Flow cytometric analysis showed that MSC inhibited the proliferation of CD4+ and CD8+ T-lymphocyte subsets in pretransplant and posttransplant donor-directed MLR, whereas MSC had no effect on B- or natural killer-cell proliferation.


CONCLUSIONS
Donor MSC significantly inhibited the proliferation of alloactivated recipient T cells before and after kidney transplantation. We believe these findings should encourage MSC-based intervention in clinical organ transplantation.
Crop
Meindert J
MJ
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. m.crop@erasmusmc.nl
Baan
Carla C
CC
Korevaar
Sander S
SS
Ijzermans
Jan N M
JN
Alwayn
Ian P J
IP
Weimar
Willem
W
Hoogduijn
Martin J
MJ
D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D000368:Aged; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D020858:Tissue and Organ Harvesting / Q000379:methods
D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies