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Stem Cells International
Volume 2015 (2015), Article ID 486141, 7 pages
http://dx.doi.org/10.1155/2015/486141
Research Article

Extracellular Vesicles from MSC Modulate the Immune Response to Renal Allografts in a MHC Disparate Rat Model

1Department of Hepatobiliary Surgery and Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
2Pediatric Nephrology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
3Clinic for Stem Cell Transplantation, Department of Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany

Received 14 June 2015; Accepted 2 August 2015

Academic Editor: Eva Mezey

Copyright © 2015 M. Koch et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Application of mesenchymal stromal cells (MSC) has been proposed for solid organ transplantation based on their potent immunomodulatory effects. Since side effects from the injection of large cells cannot be excluded, the hypothesis rises that extracellular vesicles (EV) may cause immunomodulatory effects comparable to MSC without additional side effects. We used MSC-derived EV in a rat renal transplant model for acute rejection. We analysed peripheral blood leukocytes (PBL), kidney function, graft infiltrating cells, cytokines in the graft, and alloantibody development in animals without (allo) and with EV application (allo EV). There was no difference in kidney function and in the PBL subpopulation including Tregs between allo and allo EV. In the grafts T- and B-cell numbers were significantly higher and NK-cells lower in the allo EV kidneys compared to allo. TNF-α transcription was lower in allo EV grafts compared to allo; there was no difference regarding IL-10 and in the development of alloantibodies. In conclusion, the different cell infiltrates and cytokine transcription suggest distinct immunomodulatory properties of EV in allotransplantation. While the increased T- and B-cells in the allo EV grafts may represent a missing or negative effect on the adaptive immune system, EV seem to influence the innate immune system in a contrary fashion.