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Exosome Cell Origin Affects In Vitro Markers of Tendon Repair in Ovine Macrophages and Tenocytes

Tendon injuries and disease are resistant to surgical repair; thus, adjunct therapies are widely investigated, especially mesenchymal stromal cells (MSCs) and, more recently, their extracellular vesicles (MSCdEVs), for example, exosomes. Thought to act on resident and infiltrating immune cells, the...

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Autores principales: von Stade, Devin, Meyers, Melinda, Johnson, James, Schlegel, Ted T., Romeo, Anthony, Regan, Daniel, McGilvray, Kirk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178933/
https://www.ncbi.nlm.nih.gov/pubmed/36792933
http://dx.doi.org/10.1089/ten.tea.2022.0185
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author von Stade, Devin
Meyers, Melinda
Johnson, James
Schlegel, Ted T.
Romeo, Anthony
Regan, Daniel
McGilvray, Kirk
author_facet von Stade, Devin
Meyers, Melinda
Johnson, James
Schlegel, Ted T.
Romeo, Anthony
Regan, Daniel
McGilvray, Kirk
author_sort von Stade, Devin
collection PubMed
description Tendon injuries and disease are resistant to surgical repair; thus, adjunct therapies are widely investigated, especially mesenchymal stromal cells (MSCs) and, more recently, their extracellular vesicles (MSCdEVs), for example, exosomes. Thought to act on resident and infiltrating immune cells, the role of MSCdEVs in paracrine signaling is of great interest. This study investigated how MSCdEVs differ from analogs derived from resident (tenocyte) populations (TdEV). As macrophages play a significant role in tendon maintenance and repair, macrophage signaling was compared by cytokine quantification using a multiplexed immunoassay and tenocyte migration by in vitro scratch-wound analysis. TdEV-treated macrophages decreased IL-1 and increased MIP-1 and CXCL8 expression. In addition, macrophage signaling favored collagen synthesis and tenocyte bioactivity, while reducing proangiogenic signaling when TdEVs were used in place of MSCdEVs. These in vitro data demonstrate a differential influence of exosomes on macrophage signaling, according to cell source, supporting that local cell-derived exosomes may preferentially drive healing by different means with possible different outcomes compared to MSCdEVs. IMPACT STATEMENT: Adipose-derived mesenchymal stromal cell (AdMSC) exosomes (EVs) can improve tendon mechanical resilience, tissue organization, and M2 macrophage phenotype predominance in response to tendon injury. This active area of investigation drives great interest in the function of these exosomes as adjunct therapies for tendon disease, particularly rotator cuff tendinopathy. However, little is known about the effects of EVs as a function of cell source, nor regarding their efficacy in preclinical translational ovine models. Herein we demonstrate a differential effect of exosomes as a function of cell source, tenocyte compared to AdMSCs, on macrophage signaling and tenocyte migration of ovine cells.
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spelling pubmed-101789332023-05-13 Exosome Cell Origin Affects In Vitro Markers of Tendon Repair in Ovine Macrophages and Tenocytes von Stade, Devin Meyers, Melinda Johnson, James Schlegel, Ted T. Romeo, Anthony Regan, Daniel McGilvray, Kirk Tissue Eng Part A Original Articles Tendon injuries and disease are resistant to surgical repair; thus, adjunct therapies are widely investigated, especially mesenchymal stromal cells (MSCs) and, more recently, their extracellular vesicles (MSCdEVs), for example, exosomes. Thought to act on resident and infiltrating immune cells, the role of MSCdEVs in paracrine signaling is of great interest. This study investigated how MSCdEVs differ from analogs derived from resident (tenocyte) populations (TdEV). As macrophages play a significant role in tendon maintenance and repair, macrophage signaling was compared by cytokine quantification using a multiplexed immunoassay and tenocyte migration by in vitro scratch-wound analysis. TdEV-treated macrophages decreased IL-1 and increased MIP-1 and CXCL8 expression. In addition, macrophage signaling favored collagen synthesis and tenocyte bioactivity, while reducing proangiogenic signaling when TdEVs were used in place of MSCdEVs. These in vitro data demonstrate a differential influence of exosomes on macrophage signaling, according to cell source, supporting that local cell-derived exosomes may preferentially drive healing by different means with possible different outcomes compared to MSCdEVs. IMPACT STATEMENT: Adipose-derived mesenchymal stromal cell (AdMSC) exosomes (EVs) can improve tendon mechanical resilience, tissue organization, and M2 macrophage phenotype predominance in response to tendon injury. This active area of investigation drives great interest in the function of these exosomes as adjunct therapies for tendon disease, particularly rotator cuff tendinopathy. However, little is known about the effects of EVs as a function of cell source, nor regarding their efficacy in preclinical translational ovine models. Herein we demonstrate a differential effect of exosomes as a function of cell source, tenocyte compared to AdMSCs, on macrophage signaling and tenocyte migration of ovine cells. Mary Ann Liebert, Inc., publishers 2023-05-01 2023-05-10 /pmc/articles/PMC10178933/ /pubmed/36792933 http://dx.doi.org/10.1089/ten.tea.2022.0185 Text en © Devin von Stade et al., 2023; Published by Mary Ann Liebert, Inc. https://creativecommons.org/licenses/by/4.0/This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
von Stade, Devin
Meyers, Melinda
Johnson, James
Schlegel, Ted T.
Romeo, Anthony
Regan, Daniel
McGilvray, Kirk
Exosome Cell Origin Affects In Vitro Markers of Tendon Repair in Ovine Macrophages and Tenocytes
title Exosome Cell Origin Affects In Vitro Markers of Tendon Repair in Ovine Macrophages and Tenocytes
title_full Exosome Cell Origin Affects In Vitro Markers of Tendon Repair in Ovine Macrophages and Tenocytes
title_fullStr Exosome Cell Origin Affects In Vitro Markers of Tendon Repair in Ovine Macrophages and Tenocytes
title_full_unstemmed Exosome Cell Origin Affects In Vitro Markers of Tendon Repair in Ovine Macrophages and Tenocytes
title_short Exosome Cell Origin Affects In Vitro Markers of Tendon Repair in Ovine Macrophages and Tenocytes
title_sort exosome cell origin affects in vitro markers of tendon repair in ovine macrophages and tenocytes
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10178933/
https://www.ncbi.nlm.nih.gov/pubmed/36792933
http://dx.doi.org/10.1089/ten.tea.2022.0185
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