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Harnessing extracellular vesicles to direct endochondral repair of large bone defects

Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, thes...

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Detalles Bibliográficos
Autores principales: Ferreira, E., Porter, R. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987693/
https://www.ncbi.nlm.nih.gov/pubmed/29922444
http://dx.doi.org/10.1302/2046-3758.74.BJR-2018-0006
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author Ferreira, E.
Porter, R. M.
author_facet Ferreira, E.
Porter, R. M.
author_sort Ferreira, E.
collection PubMed
description Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation. Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263–273. DOI: 10.1302/2046-3758.74.BJR-2018-0006.
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spelling pubmed-59876932018-06-19 Harnessing extracellular vesicles to direct endochondral repair of large bone defects Ferreira, E. Porter, R. M. Bone Joint Res Bone Biology Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation. Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263–273. DOI: 10.1302/2046-3758.74.BJR-2018-0006. 2018-05-05 /pmc/articles/PMC5987693/ /pubmed/29922444 http://dx.doi.org/10.1302/2046-3758.74.BJR-2018-0006 Text en © 2018 Author(s) et al. This is an open-access article distributed under the terms of the Creative Commons Attributions licence (CC-BY-NC), which permits unrestricted use, distribution, and reproduction in any medium, but not for commercial gain, provided the original author and source are credited.
spellingShingle Bone Biology
Ferreira, E.
Porter, R. M.
Harnessing extracellular vesicles to direct endochondral repair of large bone defects
title Harnessing extracellular vesicles to direct endochondral repair of large bone defects
title_full Harnessing extracellular vesicles to direct endochondral repair of large bone defects
title_fullStr Harnessing extracellular vesicles to direct endochondral repair of large bone defects
title_full_unstemmed Harnessing extracellular vesicles to direct endochondral repair of large bone defects
title_short Harnessing extracellular vesicles to direct endochondral repair of large bone defects
title_sort harnessing extracellular vesicles to direct endochondral repair of large bone defects
topic Bone Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987693/
https://www.ncbi.nlm.nih.gov/pubmed/29922444
http://dx.doi.org/10.1302/2046-3758.74.BJR-2018-0006
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