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De Novo Circulating Antidonor's Cell Antibodies During Induced Acute Rejection of Allogeneic Myofibers in Myogenic Cell Transplantation: A Study in Nonhuman Primates

BACKGROUND: Transplantation of myogenic cells has potential applications in the treatment of muscle pathologies. Excluding purely autologous cell transplantation, graft viability depends on an adequate control of acute rejection (AR). To contribute in understanding AR in this context, we analyzed wh...

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Autores principales: Skuk, Daniel, Tremblay, Jacques P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828687/
https://www.ncbi.nlm.nih.gov/pubmed/29536029
http://dx.doi.org/10.1097/TXD.0000000000000740
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author Skuk, Daniel
Tremblay, Jacques P.
author_facet Skuk, Daniel
Tremblay, Jacques P.
author_sort Skuk, Daniel
collection PubMed
description BACKGROUND: Transplantation of myogenic cells has potential applications in the treatment of muscle pathologies. Excluding purely autologous cell transplantation, graft viability depends on an adequate control of acute rejection (AR). To contribute in understanding AR in this context, we analyzed whether de novo circulating antibodies against donor’s cells are detected during induced AR of graft-derived myofibers in nonhuman primates. METHODS: We allotransplanted satellite cell-derived myoblasts in macaques immunosuppressed with tacrolimus. To induce AR of graft-derived myofibers, we administered tacrolimus for 4 weeks to allow complete myofiber formation, and then we stopped tacrolimus administration. Cell-grafted sites were biopsied at tacrolimus withdrawal and then every 2 weeks and analyzed by histology until AR completion. Blood samples were taken before immunosuppression, at tacrolimus withdrawal and then every 2 weeks to detect antibodies against the donor’s cells by flow cytometry. RESULTS: There was an increase of antibodies against the donor’s cells related to AR in all monkeys. This increase was variable in intensity, and preceded, coincided or followed the histological evidence of AR (focal accumulations of lymphocytes) and/or the loss of myofibers of donor origin, and remained until the end of the follow-up (up to 8 weeks after tacrolimus withdrawal). CONCLUSIONS: Flow cytometry detection of de novo circulating antibodies against the donor’s cells was consistently associated with AR. A clear increase in this antibody detection indicated current or recent AR. Smaller increases in comparison to the preimmunosuppression values were not associated with AR.
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spelling pubmed-58286872018-03-13 De Novo Circulating Antidonor's Cell Antibodies During Induced Acute Rejection of Allogeneic Myofibers in Myogenic Cell Transplantation: A Study in Nonhuman Primates Skuk, Daniel Tremblay, Jacques P. Transplant Direct Cell Therapy BACKGROUND: Transplantation of myogenic cells has potential applications in the treatment of muscle pathologies. Excluding purely autologous cell transplantation, graft viability depends on an adequate control of acute rejection (AR). To contribute in understanding AR in this context, we analyzed whether de novo circulating antibodies against donor’s cells are detected during induced AR of graft-derived myofibers in nonhuman primates. METHODS: We allotransplanted satellite cell-derived myoblasts in macaques immunosuppressed with tacrolimus. To induce AR of graft-derived myofibers, we administered tacrolimus for 4 weeks to allow complete myofiber formation, and then we stopped tacrolimus administration. Cell-grafted sites were biopsied at tacrolimus withdrawal and then every 2 weeks and analyzed by histology until AR completion. Blood samples were taken before immunosuppression, at tacrolimus withdrawal and then every 2 weeks to detect antibodies against the donor’s cells by flow cytometry. RESULTS: There was an increase of antibodies against the donor’s cells related to AR in all monkeys. This increase was variable in intensity, and preceded, coincided or followed the histological evidence of AR (focal accumulations of lymphocytes) and/or the loss of myofibers of donor origin, and remained until the end of the follow-up (up to 8 weeks after tacrolimus withdrawal). CONCLUSIONS: Flow cytometry detection of de novo circulating antibodies against the donor’s cells was consistently associated with AR. A clear increase in this antibody detection indicated current or recent AR. Smaller increases in comparison to the preimmunosuppression values were not associated with AR. Lippincott Williams & Wilkins 2017-10-27 /pmc/articles/PMC5828687/ /pubmed/29536029 http://dx.doi.org/10.1097/TXD.0000000000000740 Text en Copyright © 2017 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 Cell Therapy
Skuk, Daniel
Tremblay, Jacques P.
De Novo Circulating Antidonor's Cell Antibodies During Induced Acute Rejection of Allogeneic Myofibers in Myogenic Cell Transplantation: A Study in Nonhuman Primates
title De Novo Circulating Antidonor's Cell Antibodies During Induced Acute Rejection of Allogeneic Myofibers in Myogenic Cell Transplantation: A Study in Nonhuman Primates
title_full De Novo Circulating Antidonor's Cell Antibodies During Induced Acute Rejection of Allogeneic Myofibers in Myogenic Cell Transplantation: A Study in Nonhuman Primates
title_fullStr De Novo Circulating Antidonor's Cell Antibodies During Induced Acute Rejection of Allogeneic Myofibers in Myogenic Cell Transplantation: A Study in Nonhuman Primates
title_full_unstemmed De Novo Circulating Antidonor's Cell Antibodies During Induced Acute Rejection of Allogeneic Myofibers in Myogenic Cell Transplantation: A Study in Nonhuman Primates
title_short De Novo Circulating Antidonor's Cell Antibodies During Induced Acute Rejection of Allogeneic Myofibers in Myogenic Cell Transplantation: A Study in Nonhuman Primates
title_sort de novo circulating antidonor's cell antibodies during induced acute rejection of allogeneic myofibers in myogenic cell transplantation: a study in nonhuman primates
topic Cell Therapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828687/
https://www.ncbi.nlm.nih.gov/pubmed/29536029
http://dx.doi.org/10.1097/TXD.0000000000000740
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