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Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells

BACKGROUND: We hypothesized that immunomodulatory properties of mesenchymal stromal cells (MSC) may be considered for desensitization. METHODS: Autologous or allogeneic bone marrow derived MSC were infused via tail vein at 0.5 M (0.5 × 10(6)), 1 M, or 2 M cells/dose on days −2, 3, 6, 9, 12 (preventi...

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Autores principales: Zhang, Zijian, Wilson, Nancy A., Chinnadurai, Raghavan, Panzer, Sarah E., Redfield, Robert R., Reese, Shannon R., Galipeau, Jacques, Djamali, Arjang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133404/
https://www.ncbi.nlm.nih.gov/pubmed/30234156
http://dx.doi.org/10.1097/TXD.0000000000000827
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author Zhang, Zijian
Wilson, Nancy A.
Chinnadurai, Raghavan
Panzer, Sarah E.
Redfield, Robert R.
Reese, Shannon R.
Galipeau, Jacques
Djamali, Arjang
author_facet Zhang, Zijian
Wilson, Nancy A.
Chinnadurai, Raghavan
Panzer, Sarah E.
Redfield, Robert R.
Reese, Shannon R.
Galipeau, Jacques
Djamali, Arjang
author_sort Zhang, Zijian
collection PubMed
description BACKGROUND: We hypothesized that immunomodulatory properties of mesenchymal stromal cells (MSC) may be considered for desensitization. METHODS: Autologous or allogeneic bone marrow derived MSC were infused via tail vein at 0.5 M (0.5 × 10(6)), 1 M, or 2 M cells/dose on days −2, 3, 6, 9, 12 (prevention) or 14, 17, 20, 23, 26 (treatment) relative to transfusion in a Brown Norway to Lewis rat model (10 groups total, n = 6 per group). RESULTS: At 4 weeks, pooled analyses demonstrated that autologous and allogeneic MSC were equally effective in reducing IgG1 and IgG2a de novo donor-specific antibody (dnDSA, P < 0.001). Dose-response studies indicated that moderate-dose MSC (5 M total) was most effective in reducing IgG1, IgG2a, and IgG2c dnDSA (P ≤ 0.01). Time course studies determined that preventive and treatment strategies were equally effective in reducing IgG1 and IgG2a dnDSA (P ≤ 0.01). However, individual group analyses determined that moderate-dose (5 M) treatment with autologous MSC was most effective in reducing IgG1, IgG2a, and IgG2c dnDSA (P ≤ 0.01). In this group, dnDSA decreased after 1 week of treatment; regulatory B cells increased in the spleen and peripheral blood mononuclear cells; and transitional B cells increased in the spleen, peripheral blood mononuclear cells, and bone marrow (P < 0.05 for all). CONCLUSIONS: Our findings indicate that autologous MSC prevent transfusion-elicited sensitization and upregulate transitional, and regulatory B cells. Additional studies are needed to determine the biological relevance of these changes after kidney transplantation.
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spelling pubmed-61334042018-09-19 Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells Zhang, Zijian Wilson, Nancy A. Chinnadurai, Raghavan Panzer, Sarah E. Redfield, Robert R. Reese, Shannon R. Galipeau, Jacques Djamali, Arjang Transplant Direct Kidney Transplantation BACKGROUND: We hypothesized that immunomodulatory properties of mesenchymal stromal cells (MSC) may be considered for desensitization. METHODS: Autologous or allogeneic bone marrow derived MSC were infused via tail vein at 0.5 M (0.5 × 10(6)), 1 M, or 2 M cells/dose on days −2, 3, 6, 9, 12 (prevention) or 14, 17, 20, 23, 26 (treatment) relative to transfusion in a Brown Norway to Lewis rat model (10 groups total, n = 6 per group). RESULTS: At 4 weeks, pooled analyses demonstrated that autologous and allogeneic MSC were equally effective in reducing IgG1 and IgG2a de novo donor-specific antibody (dnDSA, P < 0.001). Dose-response studies indicated that moderate-dose MSC (5 M total) was most effective in reducing IgG1, IgG2a, and IgG2c dnDSA (P ≤ 0.01). Time course studies determined that preventive and treatment strategies were equally effective in reducing IgG1 and IgG2a dnDSA (P ≤ 0.01). However, individual group analyses determined that moderate-dose (5 M) treatment with autologous MSC was most effective in reducing IgG1, IgG2a, and IgG2c dnDSA (P ≤ 0.01). In this group, dnDSA decreased after 1 week of treatment; regulatory B cells increased in the spleen and peripheral blood mononuclear cells; and transitional B cells increased in the spleen, peripheral blood mononuclear cells, and bone marrow (P < 0.05 for all). CONCLUSIONS: Our findings indicate that autologous MSC prevent transfusion-elicited sensitization and upregulate transitional, and regulatory B cells. Additional studies are needed to determine the biological relevance of these changes after kidney transplantation. Lippincott Williams & Wilkins 2018-08-27 /pmc/articles/PMC6133404/ /pubmed/30234156 http://dx.doi.org/10.1097/TXD.0000000000000827 Text en Copyright © 2018 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Kidney Transplantation
Zhang, Zijian
Wilson, Nancy A.
Chinnadurai, Raghavan
Panzer, Sarah E.
Redfield, Robert R.
Reese, Shannon R.
Galipeau, Jacques
Djamali, Arjang
Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells
title Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells
title_full Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells
title_fullStr Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells
title_full_unstemmed Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells
title_short Autologous Mesenchymal Stromal Cells Prevent Transfusion-elicited Sensitization and Upregulate Transitional and Regulatory B Cells
title_sort autologous mesenchymal stromal cells prevent transfusion-elicited sensitization and upregulate transitional and regulatory b cells
topic Kidney Transplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133404/
https://www.ncbi.nlm.nih.gov/pubmed/30234156
http://dx.doi.org/10.1097/TXD.0000000000000827
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