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

Koch M, Lemke A, Lange C - Stem Cells Int (2015)

Bottom Line: In the grafts T- and B-cell numbers were significantly higher and NK-cells lower in the allo EV kidneys compared to allo.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery and Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Cell infiltrates in kidney grafts. Graft infiltrates of macrophages ((a): ED1), T-cells ((b): TCR), B-cells ((c): KiB1), and NK-cells ((d): 10/78) in the allo group compared to allo EV as cells per high power field. While macrophages were not different (a), T- and B- cells ((b), (c)) were significantly more frequent in kidneys from the allo EV group while NK-cells were reduced compared to allo (d).
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fig2: Cell infiltrates in kidney grafts. Graft infiltrates of macrophages ((a): ED1), T-cells ((b): TCR), B-cells ((c): KiB1), and NK-cells ((d): 10/78) in the allo group compared to allo EV as cells per high power field. While macrophages were not different (a), T- and B- cells ((b), (c)) were significantly more frequent in kidneys from the allo EV group while NK-cells were reduced compared to allo (d).

Mentions: In kidney grafts harvested on day 7 after transplantation, there was a massive cell infiltrate of mononuclear cells in both allo groups while there were only very few infiltrating lymphocytes in the iso group (data not shown). In allotransplanted grafts macrophages and T-cells were the most prominent infiltrating cells. No difference regarding the infiltration of macrophages (Figure 2(a)) in the allo EV and the allo group has been observed. The number of T- and B-cells was higher in the allo EV animals compared to allo (Figures 2(b) and 2(c), p = 0.004 and p < 0.0001 for T- and B-cells, resp.), while NK-cell infiltrates were reduced (Figure 2(d), p < 0.0001).


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

Koch M, Lemke A, Lange C - Stem Cells Int (2015)

Cell infiltrates in kidney grafts. Graft infiltrates of macrophages ((a): ED1), T-cells ((b): TCR), B-cells ((c): KiB1), and NK-cells ((d): 10/78) in the allo group compared to allo EV as cells per high power field. While macrophages were not different (a), T- and B- cells ((b), (c)) were significantly more frequent in kidneys from the allo EV group while NK-cells were reduced compared to allo (d).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: Cell infiltrates in kidney grafts. Graft infiltrates of macrophages ((a): ED1), T-cells ((b): TCR), B-cells ((c): KiB1), and NK-cells ((d): 10/78) in the allo group compared to allo EV as cells per high power field. While macrophages were not different (a), T- and B- cells ((b), (c)) were significantly more frequent in kidneys from the allo EV group while NK-cells were reduced compared to allo (d).
Mentions: In kidney grafts harvested on day 7 after transplantation, there was a massive cell infiltrate of mononuclear cells in both allo groups while there were only very few infiltrating lymphocytes in the iso group (data not shown). In allotransplanted grafts macrophages and T-cells were the most prominent infiltrating cells. No difference regarding the infiltration of macrophages (Figure 2(a)) in the allo EV and the allo group has been observed. The number of T- and B-cells was higher in the allo EV animals compared to allo (Figures 2(b) and 2(c), p = 0.004 and p < 0.0001 for T- and B-cells, resp.), while NK-cell infiltrates were reduced (Figure 2(d), p < 0.0001).

Bottom Line: In the grafts T- and B-cell numbers were significantly higher and NK-cells lower in the allo EV kidneys compared to allo.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery and Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

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.

No MeSH data available.


Related in: MedlinePlus