The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation
The immunomodulatory characteristics of mesenchymal stromal cells (MSCs) may lead to multifaceted strategies in rejection of organ transplantation. This study was designed to investigate, first, the effect of the donor-type MSCs from Wistar rats on the immune system of immunocompetent Lewis rats and...
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doaj-e4d25abca7c54b66a6ab7de7057ae6f32020-11-25T02:37:06ZengSAGE PublishingCell Transplantation0963-68971555-38922017-06-012610.3727/096368917X695010The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal AllotransplantationAna Merino0Elia Ripoll1Laura De Ramon2Nuria Bolaños3Montserrat Goma4Oriol Bestard5Nuria Lloberas6Josep M. Grinyo7Juan Torras Ambròs8Experimental and Translational Laboratory of Nephrology, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, SpainExperimental and Translational Laboratory of Nephrology, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, SpainExperimental and Translational Laboratory of Nephrology, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, SpainExperimental and Translational Laboratory of Nephrology, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, SpainPathology Department, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, SpainNephrology Department, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, SpainExperimental and Translational Laboratory of Nephrology, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, SpainNephrology Department, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, SpainNephrology Department, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, SpainThe immunomodulatory characteristics of mesenchymal stromal cells (MSCs) may lead to multifaceted strategies in rejection of organ transplantation. This study was designed to investigate, first, the effect of the donor-type MSCs from Wistar rats on the immune system of immunocompetent Lewis rats and, second, the rejection responses in a renal transplantation model of Wistar to Lewis. In the first experimental model, MSCs from the bone marrow induced a systemic immune response in the immunocompetent Lewis rats, characterized by two different phases. In the initial phase (days 1–3 after MSCs infusion), the main findings were a decrease in the percentage of the main peripheral blood (PB) lymphocyte subpopulations [T cells, B cells, and natural killer (NK) cells], an increase in the FOXP3 MFI in Tregs, and an elevated concentration of circulating proinflammatory cytokines (IL-1β and TNF-α). In the late phase (days 4–6), the percentage of T cells, B cells, and NK cells returned to baseline levels; the concentration of circulating IL-1β and TNF-α decreased; and the level of anti-inflammatory cytokines (IL-10 and IL-4) increased with respect to the initial phase. In the allogeneic kidney transplantation model, rats were randomized into four groups: nontreated, cyclosporine oral administration, and two groups of rats treated with two different schedules of MSC infusion: 4 days (MSCs-4) and 7 days (MSCs-7) before kidney transplantation and in both a further infusion at the day of transplantation. Both MSC treatments decreased the percentage of T, B, and NK cells in PB. Creatinine levels, survival, and histological parameters were better in MSCs-7 than in MSCs-4. We can conclude that MSCs, by themselves, produce changes in the immune system; they do not need a pathological condition to produce immunomodulatory responses. In the renal allograft model, the optimal time schedule for MSC infusion before grafting was 7 days to prevent acute rejection.https://doi.org/10.3727/096368917X695010 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ana Merino Elia Ripoll Laura De Ramon Nuria Bolaños Montserrat Goma Oriol Bestard Nuria Lloberas Josep M. Grinyo Juan Torras Ambròs |
spellingShingle |
Ana Merino Elia Ripoll Laura De Ramon Nuria Bolaños Montserrat Goma Oriol Bestard Nuria Lloberas Josep M. Grinyo Juan Torras Ambròs The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation Cell Transplantation |
author_facet |
Ana Merino Elia Ripoll Laura De Ramon Nuria Bolaños Montserrat Goma Oriol Bestard Nuria Lloberas Josep M. Grinyo Juan Torras Ambròs |
author_sort |
Ana Merino |
title |
The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation |
title_short |
The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation |
title_full |
The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation |
title_fullStr |
The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation |
title_full_unstemmed |
The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation |
title_sort |
timing of immunomodulation induced by mesenchymal stromal cells determines the outcome of the graft in experimental renal allotransplantation |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2017-06-01 |
description |
The immunomodulatory characteristics of mesenchymal stromal cells (MSCs) may lead to multifaceted strategies in rejection of organ transplantation. This study was designed to investigate, first, the effect of the donor-type MSCs from Wistar rats on the immune system of immunocompetent Lewis rats and, second, the rejection responses in a renal transplantation model of Wistar to Lewis. In the first experimental model, MSCs from the bone marrow induced a systemic immune response in the immunocompetent Lewis rats, characterized by two different phases. In the initial phase (days 1–3 after MSCs infusion), the main findings were a decrease in the percentage of the main peripheral blood (PB) lymphocyte subpopulations [T cells, B cells, and natural killer (NK) cells], an increase in the FOXP3 MFI in Tregs, and an elevated concentration of circulating proinflammatory cytokines (IL-1β and TNF-α). In the late phase (days 4–6), the percentage of T cells, B cells, and NK cells returned to baseline levels; the concentration of circulating IL-1β and TNF-α decreased; and the level of anti-inflammatory cytokines (IL-10 and IL-4) increased with respect to the initial phase. In the allogeneic kidney transplantation model, rats were randomized into four groups: nontreated, cyclosporine oral administration, and two groups of rats treated with two different schedules of MSC infusion: 4 days (MSCs-4) and 7 days (MSCs-7) before kidney transplantation and in both a further infusion at the day of transplantation. Both MSC treatments decreased the percentage of T, B, and NK cells in PB. Creatinine levels, survival, and histological parameters were better in MSCs-7 than in MSCs-4. We can conclude that MSCs, by themselves, produce changes in the immune system; they do not need a pathological condition to produce immunomodulatory responses. In the renal allograft model, the optimal time schedule for MSC infusion before grafting was 7 days to prevent acute rejection. |
url |
https://doi.org/10.3727/096368917X695010 |
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