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Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure

Upon myocardial damage, the release of cardiac proteins induces a strong antibody-mediated immune response, which can lead to adverse cardiac remodeling and eventually heart failure (HF). Stem cell therapy using mesenchymal stromal cells (MSCs) or cardiomyocyte progenitor cells (CPCs) previously sho...

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Autores principales: van den Hoogen, Patricia, de Jager, Saskia C. A., Mol, Emma A., Schoneveld, Arjan S., Huibers, Manon M. H., Vink, Aryan, Doevendans, Pieter A., Laman, Jon D., Sluijter, Joost P. G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938331/
https://www.ncbi.nlm.nih.gov/pubmed/31891633
http://dx.doi.org/10.1371/journal.pone.0227283
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author van den Hoogen, Patricia
de Jager, Saskia C. A.
Mol, Emma A.
Schoneveld, Arjan S.
Huibers, Manon M. H.
Vink, Aryan
Doevendans, Pieter A.
Laman, Jon D.
Sluijter, Joost P. G.
author_facet van den Hoogen, Patricia
de Jager, Saskia C. A.
Mol, Emma A.
Schoneveld, Arjan S.
Huibers, Manon M. H.
Vink, Aryan
Doevendans, Pieter A.
Laman, Jon D.
Sluijter, Joost P. G.
author_sort van den Hoogen, Patricia
collection PubMed
description Upon myocardial damage, the release of cardiac proteins induces a strong antibody-mediated immune response, which can lead to adverse cardiac remodeling and eventually heart failure (HF). Stem cell therapy using mesenchymal stromal cells (MSCs) or cardiomyocyte progenitor cells (CPCs) previously showed beneficial effects on cardiac function despite low engraftment in the heart. Paracrine mediators are likely of great importance, where, for example, MSC-derived extracellular vesicles (EVs) also show immunosuppressive properties in vitro. However, the limited capacity of MSCs to differentiate into cardiac cells and the sufficient scaling of MSC-derived EVs remain a challenge to clinical translation. Therefore, we investigated the immunosuppressive actions of endogenous CPCs and CPC-derived EVs on antibody production in vitro, using both healthy controls and end-stage HF patients. Both MSCs and CPCs strongly inhibit lymphocyte proliferation and antibody production in vitro. Furthermore, CPC-derived EVs significantly lowered the levels of IgG1, IgG4, and IgM, especially when administered for longer duration. In line with previous findings, plasma cells of end-stage HF patients showed high production of IgG3, which can be inhibited by MSCs in vitro. MSCs and CPCs inhibit in vitro antibody production of both healthy and end-stage HF-derived immune cells. CPC-derived paracrine factors, such as EVs, show similar effects, but do not provide the complete immunosuppressive capacity of CPCs. The strongest immunosuppressive effects were observed using MSCs, suggesting that MSCs might be the best candidates for therapeutic targeting of B-cell responses in HF.
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spelling pubmed-69383312020-01-07 Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure van den Hoogen, Patricia de Jager, Saskia C. A. Mol, Emma A. Schoneveld, Arjan S. Huibers, Manon M. H. Vink, Aryan Doevendans, Pieter A. Laman, Jon D. Sluijter, Joost P. G. PLoS One Research Article Upon myocardial damage, the release of cardiac proteins induces a strong antibody-mediated immune response, which can lead to adverse cardiac remodeling and eventually heart failure (HF). Stem cell therapy using mesenchymal stromal cells (MSCs) or cardiomyocyte progenitor cells (CPCs) previously showed beneficial effects on cardiac function despite low engraftment in the heart. Paracrine mediators are likely of great importance, where, for example, MSC-derived extracellular vesicles (EVs) also show immunosuppressive properties in vitro. However, the limited capacity of MSCs to differentiate into cardiac cells and the sufficient scaling of MSC-derived EVs remain a challenge to clinical translation. Therefore, we investigated the immunosuppressive actions of endogenous CPCs and CPC-derived EVs on antibody production in vitro, using both healthy controls and end-stage HF patients. Both MSCs and CPCs strongly inhibit lymphocyte proliferation and antibody production in vitro. Furthermore, CPC-derived EVs significantly lowered the levels of IgG1, IgG4, and IgM, especially when administered for longer duration. In line with previous findings, plasma cells of end-stage HF patients showed high production of IgG3, which can be inhibited by MSCs in vitro. MSCs and CPCs inhibit in vitro antibody production of both healthy and end-stage HF-derived immune cells. CPC-derived paracrine factors, such as EVs, show similar effects, but do not provide the complete immunosuppressive capacity of CPCs. The strongest immunosuppressive effects were observed using MSCs, suggesting that MSCs might be the best candidates for therapeutic targeting of B-cell responses in HF. Public Library of Science 2019-12-31 /pmc/articles/PMC6938331/ /pubmed/31891633 http://dx.doi.org/10.1371/journal.pone.0227283 Text en © 2019 van den Hoogen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
van den Hoogen, Patricia
de Jager, Saskia C. A.
Mol, Emma A.
Schoneveld, Arjan S.
Huibers, Manon M. H.
Vink, Aryan
Doevendans, Pieter A.
Laman, Jon D.
Sluijter, Joost P. G.
Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure
title Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure
title_full Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure
title_fullStr Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure
title_full_unstemmed Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure
title_short Potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of B-cells and antibody responses in end-stage heart failure
title_sort potential of mesenchymal- and cardiac progenitor cells for therapeutic targeting of b-cells and antibody responses in end-stage heart failure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938331/
https://www.ncbi.nlm.nih.gov/pubmed/31891633
http://dx.doi.org/10.1371/journal.pone.0227283
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