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Stem Cell-Based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1β

[Image: see text] Osteoarthritis (OA) is a chronic degenerative disease of the articular joint that involves both bone and cartilage degenerative changes. An engineered osteochondral tissue within physiological conditions will be of significant utility in understanding the pathogenesis of OA and tes...

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Autores principales: Lin, Hang, Lozito, Thomas P., Alexander, Peter G., Gottardi, Riccardo, Tuan, Rocky S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086740/
https://www.ncbi.nlm.nih.gov/pubmed/24830762
http://dx.doi.org/10.1021/mp500136b
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author Lin, Hang
Lozito, Thomas P.
Alexander, Peter G.
Gottardi, Riccardo
Tuan, Rocky S.
author_facet Lin, Hang
Lozito, Thomas P.
Alexander, Peter G.
Gottardi, Riccardo
Tuan, Rocky S.
author_sort Lin, Hang
collection PubMed
description [Image: see text] Osteoarthritis (OA) is a chronic degenerative disease of the articular joint that involves both bone and cartilage degenerative changes. An engineered osteochondral tissue within physiological conditions will be of significant utility in understanding the pathogenesis of OA and testing the efficacy of potential disease-modifying OA drugs (DMOADs). In this study, a multichamber bioreactor was fabricated and fitted into a microfluidic base. When the osteochondral construct is inserted, two chambers are formed on either side of the construct (top, chondral; bottom, osseous) that is supplied by different medium streams. These medium conduits are critical to create tissue-specific microenvironments in which chondral and osseous tissues will develop and mature. Human bone marrow stem cell (hBMSCs)-derived constructs were fabricated in situ and cultured within the bioreactor and induced to undergo spatially defined chondrogenic and osteogenic differentiation for 4 weeks in tissue-specific media. We observed tissue specific gene expression and matrix production as well as a basophilic interface suggesting a developing tidemark. Introduction of interleukin-1β (IL-1β) to either the chondral or osseous medium stream induced stronger degradative responses locally as well as in the opposing tissue type. For example, IL-1β treatment of the osseous compartment resulted in a strong catabolic response in the chondral layer as indicated by increased matrix metalloproteinase (MMP) expression and activity, and tissue-specific gene expression. This induction was greater than that seen with IL-1β application to the chondral component directly, indicative of active biochemical communication between the two tissue layers and supporting the osteochondral nature of OA. The microtissue culture system developed here offers novel capabilities for investigating the physiology of osteochondral tissue and pathogenic mechanisms of OA and serving as a high-throughput platform to test potential DMOADS.
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spelling pubmed-40867402015-05-15 Stem Cell-Based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1β Lin, Hang Lozito, Thomas P. Alexander, Peter G. Gottardi, Riccardo Tuan, Rocky S. Mol Pharm [Image: see text] Osteoarthritis (OA) is a chronic degenerative disease of the articular joint that involves both bone and cartilage degenerative changes. An engineered osteochondral tissue within physiological conditions will be of significant utility in understanding the pathogenesis of OA and testing the efficacy of potential disease-modifying OA drugs (DMOADs). In this study, a multichamber bioreactor was fabricated and fitted into a microfluidic base. When the osteochondral construct is inserted, two chambers are formed on either side of the construct (top, chondral; bottom, osseous) that is supplied by different medium streams. These medium conduits are critical to create tissue-specific microenvironments in which chondral and osseous tissues will develop and mature. Human bone marrow stem cell (hBMSCs)-derived constructs were fabricated in situ and cultured within the bioreactor and induced to undergo spatially defined chondrogenic and osteogenic differentiation for 4 weeks in tissue-specific media. We observed tissue specific gene expression and matrix production as well as a basophilic interface suggesting a developing tidemark. Introduction of interleukin-1β (IL-1β) to either the chondral or osseous medium stream induced stronger degradative responses locally as well as in the opposing tissue type. For example, IL-1β treatment of the osseous compartment resulted in a strong catabolic response in the chondral layer as indicated by increased matrix metalloproteinase (MMP) expression and activity, and tissue-specific gene expression. This induction was greater than that seen with IL-1β application to the chondral component directly, indicative of active biochemical communication between the two tissue layers and supporting the osteochondral nature of OA. The microtissue culture system developed here offers novel capabilities for investigating the physiology of osteochondral tissue and pathogenic mechanisms of OA and serving as a high-throughput platform to test potential DMOADS. American Chemical Society 2014-05-15 2014-07-07 /pmc/articles/PMC4086740/ /pubmed/24830762 http://dx.doi.org/10.1021/mp500136b Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Lin, Hang
Lozito, Thomas P.
Alexander, Peter G.
Gottardi, Riccardo
Tuan, Rocky S.
Stem Cell-Based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1β
title Stem Cell-Based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1β
title_full Stem Cell-Based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1β
title_fullStr Stem Cell-Based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1β
title_full_unstemmed Stem Cell-Based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1β
title_short Stem Cell-Based Microphysiological Osteochondral System to Model Tissue Response to Interleukin-1β
title_sort stem cell-based microphysiological osteochondral system to model tissue response to interleukin-1β
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086740/
https://www.ncbi.nlm.nih.gov/pubmed/24830762
http://dx.doi.org/10.1021/mp500136b
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