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Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell

BACKGROUND: Extracellular vesicles (EVs) produced by human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are currently investigated for their clinical effectiveness towards immune-mediated diseases. The large amounts of stem cell-derived EVs required for clinical testing suggest that bior...

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Autores principales: Gobin, Jonathan, Muradia, Gauri, Mehic, Jelica, Westwood, Carole, Couvrette, Lauren, Stalker, Andrew, Bigelow, Stewart, Luebbert, Christian C., Bissonnette, Frédéric St-Denis, Johnston, Michael J. W., Sauvé, Simon, Tam, Roger Y., Wang, Lisheng, Rosu-Myles, Michael, Lavoie, Jessie R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880218/
https://www.ncbi.nlm.nih.gov/pubmed/33579358
http://dx.doi.org/10.1186/s13287-021-02190-3
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author Gobin, Jonathan
Muradia, Gauri
Mehic, Jelica
Westwood, Carole
Couvrette, Lauren
Stalker, Andrew
Bigelow, Stewart
Luebbert, Christian C.
Bissonnette, Frédéric St-Denis
Johnston, Michael J. W.
Sauvé, Simon
Tam, Roger Y.
Wang, Lisheng
Rosu-Myles, Michael
Lavoie, Jessie R.
author_facet Gobin, Jonathan
Muradia, Gauri
Mehic, Jelica
Westwood, Carole
Couvrette, Lauren
Stalker, Andrew
Bigelow, Stewart
Luebbert, Christian C.
Bissonnette, Frédéric St-Denis
Johnston, Michael J. W.
Sauvé, Simon
Tam, Roger Y.
Wang, Lisheng
Rosu-Myles, Michael
Lavoie, Jessie R.
author_sort Gobin, Jonathan
collection PubMed
description BACKGROUND: Extracellular vesicles (EVs) produced by human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are currently investigated for their clinical effectiveness towards immune-mediated diseases. The large amounts of stem cell-derived EVs required for clinical testing suggest that bioreactor production systems may be a more amenable alternative than conventional EV production methods for manufacturing products for therapeutic use in humans. METHODS: To characterize the potential utility of these systems, EVs from four hBM-MSC donors were produced independently using a hollow-fiber bioreactor system under a cGMP-compliant procedure. EVs were harvested and characterized for size, concentration, immunophenotype, and glycan profile at three separate intervals throughout a 25-day period. RESULTS: Bioreactor-inoculated hBM-MSCs maintained high viability and retained their trilineage mesoderm differentiation capability while still expressing MSC-associated markers upon retrieval. EVs collected from the four hBM-MSC donors showed consistency in size and concentration in addition to presenting a consistent surface glycan profile. EV surface immunophenotypic analyses revealed a consistent low immunogenicity profile in addition to the presence of immuno-regulatory CD40 antigen. EV cargo analysis for biomarkers of immune regulation showed a high abundance of immuno-regulatory and angiogenic factors VEGF-A and IL-8. CONCLUSIONS: Significantly, EVs from hBM-MSCs with immuno-regulatory constituents were generated in a large-scale system over a long production period and could be frequently harvested with the same quality and quantity, which will circumvent the challenge for clinical application. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02190-3.
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spelling pubmed-78802182021-02-16 Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell Gobin, Jonathan Muradia, Gauri Mehic, Jelica Westwood, Carole Couvrette, Lauren Stalker, Andrew Bigelow, Stewart Luebbert, Christian C. Bissonnette, Frédéric St-Denis Johnston, Michael J. W. Sauvé, Simon Tam, Roger Y. Wang, Lisheng Rosu-Myles, Michael Lavoie, Jessie R. Stem Cell Res Ther Research BACKGROUND: Extracellular vesicles (EVs) produced by human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) are currently investigated for their clinical effectiveness towards immune-mediated diseases. The large amounts of stem cell-derived EVs required for clinical testing suggest that bioreactor production systems may be a more amenable alternative than conventional EV production methods for manufacturing products for therapeutic use in humans. METHODS: To characterize the potential utility of these systems, EVs from four hBM-MSC donors were produced independently using a hollow-fiber bioreactor system under a cGMP-compliant procedure. EVs were harvested and characterized for size, concentration, immunophenotype, and glycan profile at three separate intervals throughout a 25-day period. RESULTS: Bioreactor-inoculated hBM-MSCs maintained high viability and retained their trilineage mesoderm differentiation capability while still expressing MSC-associated markers upon retrieval. EVs collected from the four hBM-MSC donors showed consistency in size and concentration in addition to presenting a consistent surface glycan profile. EV surface immunophenotypic analyses revealed a consistent low immunogenicity profile in addition to the presence of immuno-regulatory CD40 antigen. EV cargo analysis for biomarkers of immune regulation showed a high abundance of immuno-regulatory and angiogenic factors VEGF-A and IL-8. CONCLUSIONS: Significantly, EVs from hBM-MSCs with immuno-regulatory constituents were generated in a large-scale system over a long production period and could be frequently harvested with the same quality and quantity, which will circumvent the challenge for clinical application. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02190-3. BioMed Central 2021-02-12 /pmc/articles/PMC7880218/ /pubmed/33579358 http://dx.doi.org/10.1186/s13287-021-02190-3 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Gobin, Jonathan
Muradia, Gauri
Mehic, Jelica
Westwood, Carole
Couvrette, Lauren
Stalker, Andrew
Bigelow, Stewart
Luebbert, Christian C.
Bissonnette, Frédéric St-Denis
Johnston, Michael J. W.
Sauvé, Simon
Tam, Roger Y.
Wang, Lisheng
Rosu-Myles, Michael
Lavoie, Jessie R.
Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell
title Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell
title_full Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell
title_fullStr Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell
title_full_unstemmed Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell
title_short Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell
title_sort hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880218/
https://www.ncbi.nlm.nih.gov/pubmed/33579358
http://dx.doi.org/10.1186/s13287-021-02190-3
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