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Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application
While mesenchymal stromal cells are an appealing therapeutic option for a range of clinical applications, their potential to induce clotting when used systemically remains a safety concern, particularly in hypercoagulable conditions, such as in patients with severe COVID‐19, trauma, or cancers. Here...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133341/ https://www.ncbi.nlm.nih.gov/pubmed/33527780 http://dx.doi.org/10.1002/sctm.20-0454 |
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author | O'Rourke, Brian Nguyen, Sunny Tilles, Arno W. Bynum, James A. Cap, Andrew P. Parekkadan, Biju Barcia, Rita N. |
author_facet | O'Rourke, Brian Nguyen, Sunny Tilles, Arno W. Bynum, James A. Cap, Andrew P. Parekkadan, Biju Barcia, Rita N. |
author_sort | O'Rourke, Brian |
collection | PubMed |
description | While mesenchymal stromal cells are an appealing therapeutic option for a range of clinical applications, their potential to induce clotting when used systemically remains a safety concern, particularly in hypercoagulable conditions, such as in patients with severe COVID‐19, trauma, or cancers. Here, we tested a novel preclinical approach aimed at improving the safety of mesenchymal stromal cell (MSC) systemic administration by use of a bioreactor. In this system, MSCs are seeded on the exterior of a hollow‐fiber filter, sequestering them behind a hemocompatible semipermeable membrane with defined pore‐size and permeability to allow for a molecularly defined cross talk between the therapeutic cells and the whole blood environment, including blood cells and signaling molecules. The potential for these bioreactor MSCs to induce clots in coagulable plasma was compared against directly injected “free” MSCs, a model of systemic administration. Our results showed that restricting MSCs exposure to plasma via a bioreactor extends the time necessary for clot formation to occur when compared with “free” MSCs. Measurement of cell surface data indicates the presence of known clot inducing factors, namely tissue factor and phosphatidylserine. Results also showed that recovering cells and flushing the bioreactor prior to use further prolonged clot formation time. Furthermore, application of this technology in two in vivo models did not require additional heparin in fully anticoagulated experimental animals to maintain target activated clotting time levels relative to heparin anticoagulated controls. Taken together the clinical use of bioreactor housed MSCs could offer a novel method to control systemic MSC exposure and prolong clot formation time. |
format | Online Article Text |
id | pubmed-8133341 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81333412021-05-21 Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application O'Rourke, Brian Nguyen, Sunny Tilles, Arno W. Bynum, James A. Cap, Andrew P. Parekkadan, Biju Barcia, Rita N. Stem Cells Transl Med Enabling Technologies for Cell‐based Clinical Translation While mesenchymal stromal cells are an appealing therapeutic option for a range of clinical applications, their potential to induce clotting when used systemically remains a safety concern, particularly in hypercoagulable conditions, such as in patients with severe COVID‐19, trauma, or cancers. Here, we tested a novel preclinical approach aimed at improving the safety of mesenchymal stromal cell (MSC) systemic administration by use of a bioreactor. In this system, MSCs are seeded on the exterior of a hollow‐fiber filter, sequestering them behind a hemocompatible semipermeable membrane with defined pore‐size and permeability to allow for a molecularly defined cross talk between the therapeutic cells and the whole blood environment, including blood cells and signaling molecules. The potential for these bioreactor MSCs to induce clots in coagulable plasma was compared against directly injected “free” MSCs, a model of systemic administration. Our results showed that restricting MSCs exposure to plasma via a bioreactor extends the time necessary for clot formation to occur when compared with “free” MSCs. Measurement of cell surface data indicates the presence of known clot inducing factors, namely tissue factor and phosphatidylserine. Results also showed that recovering cells and flushing the bioreactor prior to use further prolonged clot formation time. Furthermore, application of this technology in two in vivo models did not require additional heparin in fully anticoagulated experimental animals to maintain target activated clotting time levels relative to heparin anticoagulated controls. Taken together the clinical use of bioreactor housed MSCs could offer a novel method to control systemic MSC exposure and prolong clot formation time. John Wiley & Sons, Inc. 2021-02-01 /pmc/articles/PMC8133341/ /pubmed/33527780 http://dx.doi.org/10.1002/sctm.20-0454 Text en © 2021 The Authors. stem cells translational medicine published by Wiley Periodicals LLC on behalf of AlphaMed Press https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Enabling Technologies for Cell‐based Clinical Translation O'Rourke, Brian Nguyen, Sunny Tilles, Arno W. Bynum, James A. Cap, Andrew P. Parekkadan, Biju Barcia, Rita N. Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application |
title | Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application |
title_full | Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application |
title_fullStr | Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application |
title_full_unstemmed | Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application |
title_short | Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application |
title_sort | mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application |
topic | Enabling Technologies for Cell‐based Clinical Translation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133341/ https://www.ncbi.nlm.nih.gov/pubmed/33527780 http://dx.doi.org/10.1002/sctm.20-0454 |
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