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Mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: Implications for cytotherapy
BACKGROUND: Stem cell therapy is the next generation a well-established technique. Cell therapy with mesenchymal stem cells (MSC) has been demonstrated to enhance wound healing in diabetic mice, at least partly due to improved growth factor production. However, it is unclear whether MSC can biomecha...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629071/ https://www.ncbi.nlm.nih.gov/pubmed/31306414 http://dx.doi.org/10.1371/journal.pone.0218536 |
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author | Hilton, Sarah A. Dewberry, Lindel C. Hodges, Maggie M. Hu, Junyi Xu, Junwang Liechty, Kenneth W. Zgheib, Carlos |
author_facet | Hilton, Sarah A. Dewberry, Lindel C. Hodges, Maggie M. Hu, Junyi Xu, Junwang Liechty, Kenneth W. Zgheib, Carlos |
author_sort | Hilton, Sarah A. |
collection | PubMed |
description | BACKGROUND: Stem cell therapy is the next generation a well-established technique. Cell therapy with mesenchymal stem cells (MSC) has been demonstrated to enhance wound healing in diabetic mice, at least partly due to improved growth factor production. However, it is unclear whether MSC can biomechanically affect wound closure. Utilizing the well-established cell-populated collagen gel contraction model we investigated the interactions between MSC and the extracellular matrix. METHODS: Murine fetal liver-derived Mesenchymal Stem Cells (MSCs) or fetal Dermal Fibroblasts (DFs) were cultured in cell–populated collagen gels (CPCGs). The effect of cell density, conditioned media, growth factors (TGF-B1, FGF, PDGF-BB), cytoskeletal disruptors (colchicine, cytochalasin-D), and relative hypoxia on gel contraction were evaluated. Finally, we also measured the expression of integrin receptors and some growth factors by MSCs within the contracting gels. RESULTS: Our results show that at different densities, MSCs induced a higher gel contraction compared to DFs. Higher cell density resulted in faster and more complete contraction of CPCGs. Cytoskeletal inhibitors either inhibited or prevented MSC-mediated contraction in a dose dependent fashion. Growth factors, conditioned media from both MSC and DF, and hypoxia all influenced CPCG contraction. DISCUSSION: The results suggest that MSCs are capable of directly contributing to wound closure through matrix contraction, and they are more effective than DF. In addition, this study demonstrates the importance of how other factors such as cell concentration, cytokines, and oxygen tension can provide potential modulation of therapies to correct wound healing impairments. |
format | Online Article Text |
id | pubmed-6629071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-66290712019-07-25 Mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: Implications for cytotherapy Hilton, Sarah A. Dewberry, Lindel C. Hodges, Maggie M. Hu, Junyi Xu, Junwang Liechty, Kenneth W. Zgheib, Carlos PLoS One Research Article BACKGROUND: Stem cell therapy is the next generation a well-established technique. Cell therapy with mesenchymal stem cells (MSC) has been demonstrated to enhance wound healing in diabetic mice, at least partly due to improved growth factor production. However, it is unclear whether MSC can biomechanically affect wound closure. Utilizing the well-established cell-populated collagen gel contraction model we investigated the interactions between MSC and the extracellular matrix. METHODS: Murine fetal liver-derived Mesenchymal Stem Cells (MSCs) or fetal Dermal Fibroblasts (DFs) were cultured in cell–populated collagen gels (CPCGs). The effect of cell density, conditioned media, growth factors (TGF-B1, FGF, PDGF-BB), cytoskeletal disruptors (colchicine, cytochalasin-D), and relative hypoxia on gel contraction were evaluated. Finally, we also measured the expression of integrin receptors and some growth factors by MSCs within the contracting gels. RESULTS: Our results show that at different densities, MSCs induced a higher gel contraction compared to DFs. Higher cell density resulted in faster and more complete contraction of CPCGs. Cytoskeletal inhibitors either inhibited or prevented MSC-mediated contraction in a dose dependent fashion. Growth factors, conditioned media from both MSC and DF, and hypoxia all influenced CPCG contraction. DISCUSSION: The results suggest that MSCs are capable of directly contributing to wound closure through matrix contraction, and they are more effective than DF. In addition, this study demonstrates the importance of how other factors such as cell concentration, cytokines, and oxygen tension can provide potential modulation of therapies to correct wound healing impairments. Public Library of Science 2019-07-15 /pmc/articles/PMC6629071/ /pubmed/31306414 http://dx.doi.org/10.1371/journal.pone.0218536 Text en © 2019 Hilton 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 Hilton, Sarah A. Dewberry, Lindel C. Hodges, Maggie M. Hu, Junyi Xu, Junwang Liechty, Kenneth W. Zgheib, Carlos Mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: Implications for cytotherapy |
title | Mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: Implications for cytotherapy |
title_full | Mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: Implications for cytotherapy |
title_fullStr | Mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: Implications for cytotherapy |
title_full_unstemmed | Mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: Implications for cytotherapy |
title_short | Mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: Implications for cytotherapy |
title_sort | mesenchymal stromal cells contract collagen more efficiently than dermal fibroblasts: implications for cytotherapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629071/ https://www.ncbi.nlm.nih.gov/pubmed/31306414 http://dx.doi.org/10.1371/journal.pone.0218536 |
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