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Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients
Tacrolimus is the backbone of immunosuppressive agents to prevent transplant rejection. Paradoxically, tacrolimus is nephrotoxic, causing irreversible tubulointerstitial damage. Therefore, infusion of mesenchymal stromal cells (MSC) 6 and 7 weeks post-transplantation was assessed to facilitate withd...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326287/ https://www.ncbi.nlm.nih.gov/pubmed/37426430 http://dx.doi.org/10.3389/ti.2023.11329 |
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author | Hendriks, Sanne H. Heidt, Sebastiaan Schulz, Axel R. de Fijter, Johan W. Reinders, Marlies E. J. Koning, Frits van Kooten, Cees |
author_facet | Hendriks, Sanne H. Heidt, Sebastiaan Schulz, Axel R. de Fijter, Johan W. Reinders, Marlies E. J. Koning, Frits van Kooten, Cees |
author_sort | Hendriks, Sanne H. |
collection | PubMed |
description | Tacrolimus is the backbone of immunosuppressive agents to prevent transplant rejection. Paradoxically, tacrolimus is nephrotoxic, causing irreversible tubulointerstitial damage. Therefore, infusion of mesenchymal stromal cells (MSC) 6 and 7 weeks post-transplantation was assessed to facilitate withdrawal of tacrolimus in the randomized phase II TRITON trial. Here, we performed detailed analysis of the peripheral blood immune composition using mass cytometry to assess potential effects of MSC therapy on the immune system. We developed two metal-conjugated antibody panels containing 40 antibodies each. PBMC samples from 21 MSC-treated patients and 13 controls, obtained pre-transplant and at 24 and 52 weeks post-transplantation, were analyzed. In the MSC group at 24 weeks, 17 CD4(+) T cell clusters were increased of which 14 Th2-like clusters and three Th1/Th2-like clusters, as well as CD4+FoxP3+ Tregs. Additionally, five B cell clusters were increased, representing either class switched memory B cells or proliferating B cells. At 52 weeks, CCR7(+)CD38(+) mature B cells were decreased. Finally, eight Tc1 (effector) memory cytotoxic T cell clusters were increased. Our work provides a comprehensive account of the peripheral blood immune cell composition in kidney transplant recipients after MSC therapy and tacrolimus withdrawal. These results may help improving therapeutic strategies using MSCs with the aim to reduce the use of calcineurin inhibitors. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02057965. |
format | Online Article Text |
id | pubmed-10326287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103262872023-07-08 Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients Hendriks, Sanne H. Heidt, Sebastiaan Schulz, Axel R. de Fijter, Johan W. Reinders, Marlies E. J. Koning, Frits van Kooten, Cees Transpl Int Health Archive Tacrolimus is the backbone of immunosuppressive agents to prevent transplant rejection. Paradoxically, tacrolimus is nephrotoxic, causing irreversible tubulointerstitial damage. Therefore, infusion of mesenchymal stromal cells (MSC) 6 and 7 weeks post-transplantation was assessed to facilitate withdrawal of tacrolimus in the randomized phase II TRITON trial. Here, we performed detailed analysis of the peripheral blood immune composition using mass cytometry to assess potential effects of MSC therapy on the immune system. We developed two metal-conjugated antibody panels containing 40 antibodies each. PBMC samples from 21 MSC-treated patients and 13 controls, obtained pre-transplant and at 24 and 52 weeks post-transplantation, were analyzed. In the MSC group at 24 weeks, 17 CD4(+) T cell clusters were increased of which 14 Th2-like clusters and three Th1/Th2-like clusters, as well as CD4+FoxP3+ Tregs. Additionally, five B cell clusters were increased, representing either class switched memory B cells or proliferating B cells. At 52 weeks, CCR7(+)CD38(+) mature B cells were decreased. Finally, eight Tc1 (effector) memory cytotoxic T cell clusters were increased. Our work provides a comprehensive account of the peripheral blood immune cell composition in kidney transplant recipients after MSC therapy and tacrolimus withdrawal. These results may help improving therapeutic strategies using MSCs with the aim to reduce the use of calcineurin inhibitors. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02057965. Frontiers Media S.A. 2023-06-23 /pmc/articles/PMC10326287/ /pubmed/37426430 http://dx.doi.org/10.3389/ti.2023.11329 Text en Copyright © 2023 Hendriks, Heidt, Schulz, de Fijter, Reinders, Koning and van Kooten. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Health Archive Hendriks, Sanne H. Heidt, Sebastiaan Schulz, Axel R. de Fijter, Johan W. Reinders, Marlies E. J. Koning, Frits van Kooten, Cees Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients |
title | Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients |
title_full | Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients |
title_fullStr | Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients |
title_full_unstemmed | Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients |
title_short | Peripheral Blood Immune Cell Composition After Autologous MSC Infusion in Kidney Transplantation Recipients |
title_sort | peripheral blood immune cell composition after autologous msc infusion in kidney transplantation recipients |
topic | Health Archive |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10326287/ https://www.ncbi.nlm.nih.gov/pubmed/37426430 http://dx.doi.org/10.3389/ti.2023.11329 |
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