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Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo

The progressive loss of endogenous regenerative capacity that accompanies mammalian aging has been attributed at least in part to alterations in the extracellular matrix (ECM) composition of adult tissues. Thus, creation of a more regenerative microenvironment, analogous to embryonic morphogenesis,...

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Autores principales: Sutha, Ken, Schwartz, Zvi, Wang, Yun, Hyzy, Sharon, Boyan, Barbara D., McDevitt, Todd C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426716/
https://www.ncbi.nlm.nih.gov/pubmed/25961152
http://dx.doi.org/10.1038/srep09960
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author Sutha, Ken
Schwartz, Zvi
Wang, Yun
Hyzy, Sharon
Boyan, Barbara D.
McDevitt, Todd C.
author_facet Sutha, Ken
Schwartz, Zvi
Wang, Yun
Hyzy, Sharon
Boyan, Barbara D.
McDevitt, Todd C.
author_sort Sutha, Ken
collection PubMed
description The progressive loss of endogenous regenerative capacity that accompanies mammalian aging has been attributed at least in part to alterations in the extracellular matrix (ECM) composition of adult tissues. Thus, creation of a more regenerative microenvironment, analogous to embryonic morphogenesis, may be achieved via pluripotent embryonic stem cell (ESC) differentiation and derivation of devitalized materials as an alternative to decellularized adult tissues, such as demineralized bone matrix (DBM). Transplantation of devitalized ESC materials represents a novel approach to promote functional tissue regeneration and reduce the inherent batch-to-batch variability of allograft-derived materials. In this study, the osteoinductivity of embryoid body-derived material (EBM) was compared to DBM in a standard in vivo ectopic osteoinduction assay in nude mice. EBM derived from EBs differentiated for 10 days with osteogenic media (+β-glycerophosphate) exhibited similar osteoinductivity to active DBM (osteoinduction score = 2.50 ± 0.27 vs. 2.75 ± 0.16) based on histological scoring, and exceeded inactive DBM (1.13 ± 0.13, p < 0.005). Moreover, EBM stimulated formation of new bone, ossicles, and marrow spaces, similar to active DBM. The potent osteoinductivity of EBM demonstrates that morphogenic factors expressed by ESCs undergoing osteogenic differentiation yield a novel devitalized material capable of stimulating de novo bone formation in vivo.
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spelling pubmed-44267162015-05-21 Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo Sutha, Ken Schwartz, Zvi Wang, Yun Hyzy, Sharon Boyan, Barbara D. McDevitt, Todd C. Sci Rep Article The progressive loss of endogenous regenerative capacity that accompanies mammalian aging has been attributed at least in part to alterations in the extracellular matrix (ECM) composition of adult tissues. Thus, creation of a more regenerative microenvironment, analogous to embryonic morphogenesis, may be achieved via pluripotent embryonic stem cell (ESC) differentiation and derivation of devitalized materials as an alternative to decellularized adult tissues, such as demineralized bone matrix (DBM). Transplantation of devitalized ESC materials represents a novel approach to promote functional tissue regeneration and reduce the inherent batch-to-batch variability of allograft-derived materials. In this study, the osteoinductivity of embryoid body-derived material (EBM) was compared to DBM in a standard in vivo ectopic osteoinduction assay in nude mice. EBM derived from EBs differentiated for 10 days with osteogenic media (+β-glycerophosphate) exhibited similar osteoinductivity to active DBM (osteoinduction score = 2.50 ± 0.27 vs. 2.75 ± 0.16) based on histological scoring, and exceeded inactive DBM (1.13 ± 0.13, p < 0.005). Moreover, EBM stimulated formation of new bone, ossicles, and marrow spaces, similar to active DBM. The potent osteoinductivity of EBM demonstrates that morphogenic factors expressed by ESCs undergoing osteogenic differentiation yield a novel devitalized material capable of stimulating de novo bone formation in vivo. Nature Publishing Group 2015-05-11 /pmc/articles/PMC4426716/ /pubmed/25961152 http://dx.doi.org/10.1038/srep09960 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Sutha, Ken
Schwartz, Zvi
Wang, Yun
Hyzy, Sharon
Boyan, Barbara D.
McDevitt, Todd C.
Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo
title Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo
title_full Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo
title_fullStr Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo
title_full_unstemmed Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo
title_short Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo
title_sort osteogenic embryoid body-derived material induces bone formation in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426716/
https://www.ncbi.nlm.nih.gov/pubmed/25961152
http://dx.doi.org/10.1038/srep09960
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