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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2018
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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. |
format | Online Article Text |
id | pubmed-6133404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
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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