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Stem cell-based microphysiological osteochondral system to model tissue response to interleukin-1β.

Identifieur interne : 002481 ( PubMed/Curation ); précédent : 002480; suivant : 002482

Stem cell-based microphysiological osteochondral system to model tissue response to interleukin-1β.

Auteurs : Hang Lin [États-Unis] ; Thomas P. Lozito ; Peter G. Alexander ; Riccardo Gottardi ; Rocky S. Tuan

Source :

Molecular pharmaceutics [ 1543-8392 ] ; 2014.

RBID : pubmed:24830762

Descripteurs français

English descriptors

KwdEn :
- Adult, Aged, Basophils (metabolism), Basophils (physiology), Bioreactors, Cartilage, Articular (metabolism), Cartilage, Articular (physiology), Cell Differentiation (genetics), Cell Differentiation (physiology), Cells, Cultured, Chondrogenesis (genetics), Chondrogenesis (physiology), Female, Gene Expression (genetics), Humans, Interleukin-1beta (genetics), Interleukin-1beta (metabolism), Matrix Metalloproteinases (genetics), Matrix Metalloproteinases (metabolism), Middle Aged, Osteogenesis (genetics), Osteogenesis (physiology), Stem Cells (metabolism), Stem Cells (physiology), Tissue Engineering (methods).
MESH :
- chemical , genetics : Interleukin-1beta, Matrix Metalloproteinases.
- genetics : Cell Differentiation, Chondrogenesis, Gene Expression, Osteogenesis.
- metabolism : Basophils, Cartilage, Articular, Interleukin-1beta, Matrix Metalloproteinases, Stem Cells.
- methods : Tissue Engineering.
- physiology : Basophils, Cartilage, Articular, Cell Differentiation, Chondrogenesis, Osteogenesis, Stem Cells.
- Adult, Aged, Bioreactors, Cells, Cultured, Female, Humans, Middle Aged.

Abstract

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.

DOI: 10.1021/mp500136b
PubMed: 24830762

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Le document en format XML

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<term>Aged</term>
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<term>Basophils (physiology)</term>
<term>Bioreactors</term>
<term>Cartilage, Articular (metabolism)</term>
<term>Cartilage, Articular (physiology)</term>
<term>Cell Differentiation (genetics)</term>
<term>Cell Differentiation (physiology)</term>
<term>Cells, Cultured</term>
<term>Chondrogenesis (genetics)</term>
<term>Chondrogenesis (physiology)</term>
<term>Female</term>
<term>Gene Expression (genetics)</term>
<term>Humans</term>
<term>Interleukin-1beta (genetics)</term>
<term>Interleukin-1beta (metabolism)</term>
<term>Matrix Metalloproteinases (genetics)</term>
<term>Matrix Metalloproteinases (metabolism)</term>
<term>Middle Aged</term>
<term>Osteogenesis (genetics)</term>
<term>Osteogenesis (physiology)</term>
<term>Stem Cells (metabolism)</term>
<term>Stem Cells (physiology)</term>
<term>Tissue Engineering (methods)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Bioréacteurs</term>
<term>Cartilage articulaire (métabolisme)</term>
<term>Cartilage articulaire (physiologie)</term>
<term>Cellules cultivées</term>
<term>Cellules souches (métabolisme)</term>
<term>Cellules souches (physiologie)</term>
<term>Chondrogenèse (génétique)</term>
<term>Chondrogenèse (physiologie)</term>
<term>Différenciation cellulaire (génétique)</term>
<term>Différenciation cellulaire (physiologie)</term>
<term>Expression des gènes (génétique)</term>
<term>Femelle</term>
<term>Granulocytes basophiles (métabolisme)</term>
<term>Granulocytes basophiles (physiologie)</term>
<term>Humains</term>
<term>Ingénierie tissulaire ()</term>
<term>Interleukine-1 bêta (génétique)</term>
<term>Interleukine-1 bêta (métabolisme)</term>
<term>Matrix metalloproteinases (génétique)</term>
<term>Matrix metalloproteinases (métabolisme)</term>
<term>Ostéogenèse (génétique)</term>
<term>Ostéogenèse (physiologie)</term>
<term>Sujet âgé</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Interleukin-1beta</term>
<term>Matrix Metalloproteinases</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cell Differentiation</term>
<term>Chondrogenesis</term>
<term>Gene Expression</term>
<term>Osteogenesis</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Chondrogenèse</term>
<term>Différenciation cellulaire</term>
<term>Expression des gènes</term>
<term>Interleukine-1 bêta</term>
<term>Matrix metalloproteinases</term>
<term>Ostéogenèse</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Basophils</term>
<term>Cartilage, Articular</term>
<term>Interleukin-1beta</term>
<term>Matrix Metalloproteinases</term>
<term>Stem Cells</term>
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<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Tissue Engineering</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cartilage articulaire</term>
<term>Cellules souches</term>
<term>Granulocytes basophiles</term>
<term>Interleukine-1 bêta</term>
<term>Matrix metalloproteinases</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Cartilage articulaire</term>
<term>Cellules souches</term>
<term>Chondrogenèse</term>
<term>Différenciation cellulaire</term>
<term>Granulocytes basophiles</term>
<term>Ostéogenèse</term>
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<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Basophils</term>
<term>Cartilage, Articular</term>
<term>Cell Differentiation</term>
<term>Chondrogenesis</term>
<term>Osteogenesis</term>
<term>Stem Cells</term>
</keywords>
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<term>Aged</term>
<term>Bioreactors</term>
<term>Cells, Cultured</term>
<term>Female</term>
<term>Humans</term>
<term>Middle Aged</term>
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<term>Adulte d'âge moyen</term>
<term>Bioréacteurs</term>
<term>Cellules cultivées</term>
<term>Femelle</term>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
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<Abstract><AbstractText>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.</AbstractText>
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<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lin</LastName>
<ForeName>Hang</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15219, United States.</Affiliation>
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<Author ValidYN="Y"><LastName>Alexander</LastName>
<ForeName>Peter G</ForeName>
<Initials>PG</Initials>
</Author>
<Author ValidYN="Y"><LastName>Gottardi</LastName>
<ForeName>Riccardo</ForeName>
<Initials>R</Initials>
</Author>
<Author ValidYN="Y"><LastName>Tuan</LastName>
<ForeName>Rocky S</ForeName>
<Initials>RS</Initials>
</Author>
</AuthorList>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001491" MajorTopicYN="N">Basophils</DescriptorName>
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{{Explor lien
   |wiki=    Wicri/Amérique
   |area=    PittsburghV1
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   |type=    RBID
   |clé=     pubmed:24830762
   |texte=   Stem cell-based microphysiological osteochondral system to model tissue response to interleukin-1β.
}}

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Stem cell-based microphysiological osteochondral system to model tissue response to interleukin-1β.

Stem cell-based microphysiological osteochondral system to model tissue response to interleukin-1β.

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