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Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities

Approximately 10% of fractures will not heal without intervention. Current treatments can be marginally effective, costly, and some have adverse effects. A safe and manufacturable mimic of anabolic bone is the primary goal of bone engineering, but achieving this is challenging. Mesenchymal stem cell...

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Autores principales: McNeill, Eoin P., Zeitouni, Suzanne, Pan, Simin, Haskell, Andrew, Cesarek, Michael, Tahan, Daniel, Clough, Bret H., Krause, Ulf, Dobson, Lauren K., Garcia, Mayra, Kung, Christopher, Zhao, Qingguo, Saunders, W. Brian, Liu, Fei, Kaunas, Roland, Gregory, Carl A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295745/
https://www.ncbi.nlm.nih.gov/pubmed/32541821
http://dx.doi.org/10.1038/s41467-020-16646-2
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author McNeill, Eoin P.
Zeitouni, Suzanne
Pan, Simin
Haskell, Andrew
Cesarek, Michael
Tahan, Daniel
Clough, Bret H.
Krause, Ulf
Dobson, Lauren K.
Garcia, Mayra
Kung, Christopher
Zhao, Qingguo
Saunders, W. Brian
Liu, Fei
Kaunas, Roland
Gregory, Carl A.
author_facet McNeill, Eoin P.
Zeitouni, Suzanne
Pan, Simin
Haskell, Andrew
Cesarek, Michael
Tahan, Daniel
Clough, Bret H.
Krause, Ulf
Dobson, Lauren K.
Garcia, Mayra
Kung, Christopher
Zhao, Qingguo
Saunders, W. Brian
Liu, Fei
Kaunas, Roland
Gregory, Carl A.
author_sort McNeill, Eoin P.
collection PubMed
description Approximately 10% of fractures will not heal without intervention. Current treatments can be marginally effective, costly, and some have adverse effects. A safe and manufacturable mimic of anabolic bone is the primary goal of bone engineering, but achieving this is challenging. Mesenchymal stem cells (MSCs), are excellent candidates for engineering bone, but lack reproducibility due to donor source and culture methodology. The need for a bioactive attachment substrate also hinders progress. Herein, we describe a highly osteogenic MSC line generated from induced pluripotent stem cells that generates high yields of an osteogenic cell-matrix (ihOCM) in vitro. In mice, the intrinsic osteogenic activity of ihOCM surpasses bone morphogenic protein 2 (BMP2) driving healing of calvarial defects in 4 weeks by a mechanism mediated in part by collagen VI and XII. We propose that ihOCM may represent an effective replacement for autograft and BMP products used commonly in bone tissue engineering.
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spelling pubmed-72957452020-06-19 Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities McNeill, Eoin P. Zeitouni, Suzanne Pan, Simin Haskell, Andrew Cesarek, Michael Tahan, Daniel Clough, Bret H. Krause, Ulf Dobson, Lauren K. Garcia, Mayra Kung, Christopher Zhao, Qingguo Saunders, W. Brian Liu, Fei Kaunas, Roland Gregory, Carl A. Nat Commun Article Approximately 10% of fractures will not heal without intervention. Current treatments can be marginally effective, costly, and some have adverse effects. A safe and manufacturable mimic of anabolic bone is the primary goal of bone engineering, but achieving this is challenging. Mesenchymal stem cells (MSCs), are excellent candidates for engineering bone, but lack reproducibility due to donor source and culture methodology. The need for a bioactive attachment substrate also hinders progress. Herein, we describe a highly osteogenic MSC line generated from induced pluripotent stem cells that generates high yields of an osteogenic cell-matrix (ihOCM) in vitro. In mice, the intrinsic osteogenic activity of ihOCM surpasses bone morphogenic protein 2 (BMP2) driving healing of calvarial defects in 4 weeks by a mechanism mediated in part by collagen VI and XII. We propose that ihOCM may represent an effective replacement for autograft and BMP products used commonly in bone tissue engineering. Nature Publishing Group UK 2020-06-15 /pmc/articles/PMC7295745/ /pubmed/32541821 http://dx.doi.org/10.1038/s41467-020-16646-2 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
McNeill, Eoin P.
Zeitouni, Suzanne
Pan, Simin
Haskell, Andrew
Cesarek, Michael
Tahan, Daniel
Clough, Bret H.
Krause, Ulf
Dobson, Lauren K.
Garcia, Mayra
Kung, Christopher
Zhao, Qingguo
Saunders, W. Brian
Liu, Fei
Kaunas, Roland
Gregory, Carl A.
Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities
title Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities
title_full Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities
title_fullStr Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities
title_full_unstemmed Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities
title_short Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities
title_sort characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative capabilities
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295745/
https://www.ncbi.nlm.nih.gov/pubmed/32541821
http://dx.doi.org/10.1038/s41467-020-16646-2
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