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, 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. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Ana Merino [verfasserIn] Elia Ripoll [verfasserIn] Laura De Ramon [verfasserIn] Nuria Bolaños [verfasserIn] Montserrat Goma [verfasserIn] Oriol Bestard [verfasserIn] Nuria Lloberas [verfasserIn] Josep M. Grinyo [verfasserIn] Juan Torras Ambròs [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Übergeordnetes Werk:	In: Cell Transplantation - SAGE Publishing, 2017, 26(2017)
Übergeordnetes Werk:	volume:26 ; year:2017

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3727/096368917X695010

Katalog-ID:	DOAJ040263517

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allfields	10.3727/096368917X695010 doi (DE-627)DOAJ040263517 (DE-599)DOAJe4d25abca7c54b66a6ab7de7057ae6f3 DE-627 ger DE-627 rakwb eng Ana Merino verfasserin aut The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Elia Ripoll verfasserin aut Laura De Ramon verfasserin aut Nuria Bolaños verfasserin aut Montserrat Goma verfasserin aut Oriol Bestard verfasserin aut Nuria Lloberas verfasserin aut Josep M. Grinyo verfasserin aut Juan Torras Ambròs verfasserin aut In Cell Transplantation SAGE Publishing, 2017 26(2017) (DE-627)320603504 (DE-600)2020466-8 15553892 nnns volume:26 year:2017 https://doi.org/10.3727/096368917X695010 kostenfrei https://doaj.org/article/e4d25abca7c54b66a6ab7de7057ae6f3 kostenfrei https://doi.org/10.3727/096368917X695010 kostenfrei https://doaj.org/toc/0963-6897 Journal toc kostenfrei https://doaj.org/toc/1555-3892 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2017
spelling	10.3727/096368917X695010 doi (DE-627)DOAJ040263517 (DE-599)DOAJe4d25abca7c54b66a6ab7de7057ae6f3 DE-627 ger DE-627 rakwb eng Ana Merino verfasserin aut The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Elia Ripoll verfasserin aut Laura De Ramon verfasserin aut Nuria Bolaños verfasserin aut Montserrat Goma verfasserin aut Oriol Bestard verfasserin aut Nuria Lloberas verfasserin aut Josep M. Grinyo verfasserin aut Juan Torras Ambròs verfasserin aut In Cell Transplantation SAGE Publishing, 2017 26(2017) (DE-627)320603504 (DE-600)2020466-8 15553892 nnns volume:26 year:2017 https://doi.org/10.3727/096368917X695010 kostenfrei https://doaj.org/article/e4d25abca7c54b66a6ab7de7057ae6f3 kostenfrei https://doi.org/10.3727/096368917X695010 kostenfrei https://doaj.org/toc/0963-6897 Journal toc kostenfrei https://doaj.org/toc/1555-3892 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2017
allfields_unstemmed	10.3727/096368917X695010 doi (DE-627)DOAJ040263517 (DE-599)DOAJe4d25abca7c54b66a6ab7de7057ae6f3 DE-627 ger DE-627 rakwb eng Ana Merino verfasserin aut The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Elia Ripoll verfasserin aut Laura De Ramon verfasserin aut Nuria Bolaños verfasserin aut Montserrat Goma verfasserin aut Oriol Bestard verfasserin aut Nuria Lloberas verfasserin aut Josep M. Grinyo verfasserin aut Juan Torras Ambròs verfasserin aut In Cell Transplantation SAGE Publishing, 2017 26(2017) (DE-627)320603504 (DE-600)2020466-8 15553892 nnns volume:26 year:2017 https://doi.org/10.3727/096368917X695010 kostenfrei https://doaj.org/article/e4d25abca7c54b66a6ab7de7057ae6f3 kostenfrei https://doi.org/10.3727/096368917X695010 kostenfrei https://doaj.org/toc/0963-6897 Journal toc kostenfrei https://doaj.org/toc/1555-3892 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2017
allfieldsGer	10.3727/096368917X695010 doi (DE-627)DOAJ040263517 (DE-599)DOAJe4d25abca7c54b66a6ab7de7057ae6f3 DE-627 ger DE-627 rakwb eng Ana Merino verfasserin aut The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Elia Ripoll verfasserin aut Laura De Ramon verfasserin aut Nuria Bolaños verfasserin aut Montserrat Goma verfasserin aut Oriol Bestard verfasserin aut Nuria Lloberas verfasserin aut Josep M. Grinyo verfasserin aut Juan Torras Ambròs verfasserin aut In Cell Transplantation SAGE Publishing, 2017 26(2017) (DE-627)320603504 (DE-600)2020466-8 15553892 nnns volume:26 year:2017 https://doi.org/10.3727/096368917X695010 kostenfrei https://doaj.org/article/e4d25abca7c54b66a6ab7de7057ae6f3 kostenfrei https://doi.org/10.3727/096368917X695010 kostenfrei https://doaj.org/toc/0963-6897 Journal toc kostenfrei https://doaj.org/toc/1555-3892 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2017
allfieldsSound	10.3727/096368917X695010 doi (DE-627)DOAJ040263517 (DE-599)DOAJe4d25abca7c54b66a6ab7de7057ae6f3 DE-627 ger DE-627 rakwb eng Ana Merino verfasserin aut The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Medicine R Elia Ripoll verfasserin aut Laura De Ramon verfasserin aut Nuria Bolaños verfasserin aut Montserrat Goma verfasserin aut Oriol Bestard verfasserin aut Nuria Lloberas verfasserin aut Josep M. Grinyo verfasserin aut Juan Torras Ambròs verfasserin aut In Cell Transplantation SAGE Publishing, 2017 26(2017) (DE-627)320603504 (DE-600)2020466-8 15553892 nnns volume:26 year:2017 https://doi.org/10.3727/096368917X695010 kostenfrei https://doaj.org/article/e4d25abca7c54b66a6ab7de7057ae6f3 kostenfrei https://doi.org/10.3727/096368917X695010 kostenfrei https://doaj.org/toc/0963-6897 Journal toc kostenfrei https://doaj.org/toc/1555-3892 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2704 GBV_ILN_2707 GBV_ILN_2890 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 26 2017
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authorswithroles_txt_mv	Ana Merino @@aut@@ Elia Ripoll @@aut@@ Laura De Ramon @@aut@@ Nuria Bolaños @@aut@@ Montserrat Goma @@aut@@ Oriol Bestard @@aut@@ Nuria Lloberas @@aut@@ Josep M. Grinyo @@aut@@ Juan Torras Ambròs @@aut@@
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title	The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation
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title_full	The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation
author_sort	Ana Merino
journal	Cell Transplantation
journalStr	Cell Transplantation
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author_browse	Ana Merino Elia Ripoll Laura De Ramon Nuria Bolaños Montserrat Goma Oriol Bestard Nuria Lloberas Josep M. Grinyo Juan Torras Ambròs
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title_sort	timing of immunomodulation induced by mesenchymal stromal cells determines the outcome of the graft in experimental renal allotransplantation
title_auth	The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation
url	https://doi.org/10.3727/096368917X695010 https://doaj.org/article/e4d25abca7c54b66a6ab7de7057ae6f3 https://doaj.org/toc/0963-6897 https://doaj.org/toc/1555-3892
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author2	Elia Ripoll Laura De Ramon Nuria Bolaños Montserrat Goma Oriol Bestard Nuria Lloberas Josep M. Grinyo Juan Torras Ambròs
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doi_str	10.3727/096368917X695010
up_date	2024-07-03T13:53:16.783Z
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The Timing of Immunomodulation Induced by Mesenchymal Stromal Cells Determines the Outcome of the Graft in Experimental Renal Allotransplantation

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