In vitro model of vascularized bone: synergizing vascular development and osteogenesis.

Tissue engineering provides unique opportunities for regenerating diseased or damaged tissues using cells obtained from tissue biopsies. Tissue engineered grafts can also be used as high fidelity models to probe cellular and molecular interactions underlying developmental processes. In this study, w...

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Autores principales: Cristina Correia, Warren L Grayson, Miri Park, Daphne Hutton, Bin Zhou, X Edward Guo, Laura Niklason, Rui A Sousa, Rui L Reis, Gordana Vunjak-Novakovic
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Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/f090df39d2cf4e2aa0bf0f97f6a5ac63
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spelling oai:doaj.org-article:f090df39d2cf4e2aa0bf0f97f6a5ac632021-11-18T07:33:07ZIn vitro model of vascularized bone: synergizing vascular development and osteogenesis.1932-620310.1371/journal.pone.0028352https://doaj.org/article/f090df39d2cf4e2aa0bf0f97f6a5ac632011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22164277/?tool=EBIhttps://doaj.org/toc/1932-6203Tissue engineering provides unique opportunities for regenerating diseased or damaged tissues using cells obtained from tissue biopsies. Tissue engineered grafts can also be used as high fidelity models to probe cellular and molecular interactions underlying developmental processes. In this study, we co-cultured human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (MSCs) under various environmental conditions to elicit synergistic interactions leading to the colocalized development of capillary-like and bone-like tissues. Cells were encapsulated at the 1:1 ratio in fibrin gel to screen compositions of endothelial growth medium (EGM) and osteogenic medium (OM). It was determined that, to form both tissues, co-cultures should first be supplied with EGM followed by a 1:1 cocktail of the two media types containing bone morphogenetic protein-2. Subsequent studies of HUVECs and MSCs cultured in decellularized, trabecular bone scaffolds for 6 weeks assessed the effects on tissue construct of both temporal variations in growth-factor availability and addition of fresh cells. The resulting grafts were implanted subcutaneously into nude mice to determine the phenotype stability and functionality of engineered vessels. Two important findings resulted from these studies: (i) vascular development needs to be induced prior to osteogenesis, and (ii) the addition of additional hMSCs at the osteogenic induction stage improves both tissue outcomes, as shown by increased bone volume fraction, osteoid deposition, close proximity of bone proteins to vascular networks, and anastomosis of vascular networks with the host vasculature. Interestingly, these observations compare well with what has been described for native development. We propose that our cultivation system can mimic various aspects of endothelial cell-osteogenic precursor interactions in vivo, and could find utility as a model for studies of heterotypic cellular interactions that couple blood vessel formation with osteogenesis.Cristina CorreiaWarren L GraysonMiri ParkDaphne HuttonBin ZhouX Edward GuoLaura NiklasonRui A SousaRui L ReisGordana Vunjak-NovakovicPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28352 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Cristina Correia
Warren L Grayson
Miri Park
Daphne Hutton
Bin Zhou
X Edward Guo
Laura Niklason
Rui A Sousa
Rui L Reis
Gordana Vunjak-Novakovic
In vitro model of vascularized bone: synergizing vascular development and osteogenesis.
description Tissue engineering provides unique opportunities for regenerating diseased or damaged tissues using cells obtained from tissue biopsies. Tissue engineered grafts can also be used as high fidelity models to probe cellular and molecular interactions underlying developmental processes. In this study, we co-cultured human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (MSCs) under various environmental conditions to elicit synergistic interactions leading to the colocalized development of capillary-like and bone-like tissues. Cells were encapsulated at the 1:1 ratio in fibrin gel to screen compositions of endothelial growth medium (EGM) and osteogenic medium (OM). It was determined that, to form both tissues, co-cultures should first be supplied with EGM followed by a 1:1 cocktail of the two media types containing bone morphogenetic protein-2. Subsequent studies of HUVECs and MSCs cultured in decellularized, trabecular bone scaffolds for 6 weeks assessed the effects on tissue construct of both temporal variations in growth-factor availability and addition of fresh cells. The resulting grafts were implanted subcutaneously into nude mice to determine the phenotype stability and functionality of engineered vessels. Two important findings resulted from these studies: (i) vascular development needs to be induced prior to osteogenesis, and (ii) the addition of additional hMSCs at the osteogenic induction stage improves both tissue outcomes, as shown by increased bone volume fraction, osteoid deposition, close proximity of bone proteins to vascular networks, and anastomosis of vascular networks with the host vasculature. Interestingly, these observations compare well with what has been described for native development. We propose that our cultivation system can mimic various aspects of endothelial cell-osteogenic precursor interactions in vivo, and could find utility as a model for studies of heterotypic cellular interactions that couple blood vessel formation with osteogenesis.
format article
author Cristina Correia
Warren L Grayson
Miri Park
Daphne Hutton
Bin Zhou
X Edward Guo
Laura Niklason
Rui A Sousa
Rui L Reis
Gordana Vunjak-Novakovic
author_facet Cristina Correia
Warren L Grayson
Miri Park
Daphne Hutton
Bin Zhou
X Edward Guo
Laura Niklason
Rui A Sousa
Rui L Reis
Gordana Vunjak-Novakovic
author_sort Cristina Correia
title In vitro model of vascularized bone: synergizing vascular development and osteogenesis.
title_short In vitro model of vascularized bone: synergizing vascular development and osteogenesis.
title_full In vitro model of vascularized bone: synergizing vascular development and osteogenesis.
title_fullStr In vitro model of vascularized bone: synergizing vascular development and osteogenesis.
title_full_unstemmed In vitro model of vascularized bone: synergizing vascular development and osteogenesis.
title_sort in vitro model of vascularized bone: synergizing vascular development and osteogenesis.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/f090df39d2cf4e2aa0bf0f97f6a5ac63
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