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Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities

Stem cell therapies are limited by poor cell survival and engraftment. A hurdle to the use of materials for cell delivery is the lack of understanding of material properties that govern transplanted stem cell functionality. Here, we show that synthetic hydrogels presenting integrin-specific peptides...

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Autores principales: Clark, Amy Y., Martin, Karen E., García, José R., Johnson, Christopher T., Theriault, Hannah S., Han, Woojin M., Zhou, Dennis W., Botchwey, Edward A., García, Andrés J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949269/
https://www.ncbi.nlm.nih.gov/pubmed/31913286
http://dx.doi.org/10.1038/s41467-019-14000-9
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author Clark, Amy Y.
Martin, Karen E.
García, José R.
Johnson, Christopher T.
Theriault, Hannah S.
Han, Woojin M.
Zhou, Dennis W.
Botchwey, Edward A.
García, Andrés J.
author_facet Clark, Amy Y.
Martin, Karen E.
García, José R.
Johnson, Christopher T.
Theriault, Hannah S.
Han, Woojin M.
Zhou, Dennis W.
Botchwey, Edward A.
García, Andrés J.
author_sort Clark, Amy Y.
collection PubMed
description Stem cell therapies are limited by poor cell survival and engraftment. A hurdle to the use of materials for cell delivery is the lack of understanding of material properties that govern transplanted stem cell functionality. Here, we show that synthetic hydrogels presenting integrin-specific peptides enhance the survival, persistence, and osteo-reparative functions of human bone marrow-derived mesenchymal stem cells (hMSCs) transplanted in murine bone defects. Integrin-specific hydrogels regulate hMSC adhesion, paracrine signaling, and osteoblastic differentiation in vitro. Hydrogels presenting GFOGER, a peptide targeting α2β1 integrin, prolong hMSC survival and engraftment in a segmental bone defect and result in improved bone repair compared to other peptides. Integrin-specific hydrogels have diverse pleiotropic effects on hMSC reparative activities, modulating in vitro cytokine secretion and in vivo gene expression for effectors associated with inflammation, vascularization, and bone formation. These results demonstrate that integrin-specific hydrogels improve tissue healing by directing hMSC survival, engraftment, and reparative activities.
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spelling pubmed-69492692020-01-10 Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities Clark, Amy Y. Martin, Karen E. García, José R. Johnson, Christopher T. Theriault, Hannah S. Han, Woojin M. Zhou, Dennis W. Botchwey, Edward A. García, Andrés J. Nat Commun Article Stem cell therapies are limited by poor cell survival and engraftment. A hurdle to the use of materials for cell delivery is the lack of understanding of material properties that govern transplanted stem cell functionality. Here, we show that synthetic hydrogels presenting integrin-specific peptides enhance the survival, persistence, and osteo-reparative functions of human bone marrow-derived mesenchymal stem cells (hMSCs) transplanted in murine bone defects. Integrin-specific hydrogels regulate hMSC adhesion, paracrine signaling, and osteoblastic differentiation in vitro. Hydrogels presenting GFOGER, a peptide targeting α2β1 integrin, prolong hMSC survival and engraftment in a segmental bone defect and result in improved bone repair compared to other peptides. Integrin-specific hydrogels have diverse pleiotropic effects on hMSC reparative activities, modulating in vitro cytokine secretion and in vivo gene expression for effectors associated with inflammation, vascularization, and bone formation. These results demonstrate that integrin-specific hydrogels improve tissue healing by directing hMSC survival, engraftment, and reparative activities. Nature Publishing Group UK 2020-01-08 /pmc/articles/PMC6949269/ /pubmed/31913286 http://dx.doi.org/10.1038/s41467-019-14000-9 Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Clark, Amy Y.
Martin, Karen E.
García, José R.
Johnson, Christopher T.
Theriault, Hannah S.
Han, Woojin M.
Zhou, Dennis W.
Botchwey, Edward A.
García, Andrés J.
Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities
title Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities
title_full Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities
title_fullStr Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities
title_full_unstemmed Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities
title_short Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities
title_sort integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949269/
https://www.ncbi.nlm.nih.gov/pubmed/31913286
http://dx.doi.org/10.1038/s41467-019-14000-9
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