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Analysis of the Intrinsic Self-Organising Properties of Mesenchymal Stromal Cells in Three-Dimensional Co-Culture Models with Endothelial Cells

Mesenchymal stem/stromal cells (MSCs) are typically characterised by their ability to differentiate into skeletal (osteogenic, chondrogenic and adipogenic) lineages. MSCs also appear to have additional non-stem cell functions in coordinating tissue morphogenesis and organising vascular networks thro...

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Autores principales: Marshall, Julia, Barnes, Amanda, Genever, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315484/
https://www.ncbi.nlm.nih.gov/pubmed/30373192
http://dx.doi.org/10.3390/bioengineering5040092
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author Marshall, Julia
Barnes, Amanda
Genever, Paul
author_facet Marshall, Julia
Barnes, Amanda
Genever, Paul
author_sort Marshall, Julia
collection PubMed
description Mesenchymal stem/stromal cells (MSCs) are typically characterised by their ability to differentiate into skeletal (osteogenic, chondrogenic and adipogenic) lineages. MSCs also appear to have additional non-stem cell functions in coordinating tissue morphogenesis and organising vascular networks through interactions with endothelial cells (ECs). However, suitable experimental models to examine these apparently unique MSC properties are lacking. Following previous work, we have developed our 3D in vitro co-culture models to enable us to track cellular self-organisation events in heterotypic cell spheroids combining ECs, MSCs and their differentiated progeny. In these systems, MSCs, but not related fibroblastic cell types, promote the assembly of ECs into interconnected networks through intrinsic mechanisms, dependent on the relative abundance of MSC and EC numbers. Perturbation of endogenous platelet-derived growth factor (PDGF) signalling significantly increased EC network length, width and branching. When MSCs were pre-differentiated towards an osteogenic or chondrogenic lineage and co-cultured as mixed 3D spheroids, they segregated into polarised osseous and chondral regions. In the presence of ECs, the pre-differentiated MSCs redistributed to form a central mixed cell core with an outer osseous layer. Our findings demonstrate the intrinsic self-organising properties of MSCs, which may broaden their use in regenerative medicine and advance current approaches.
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spelling pubmed-63154842019-01-10 Analysis of the Intrinsic Self-Organising Properties of Mesenchymal Stromal Cells in Three-Dimensional Co-Culture Models with Endothelial Cells Marshall, Julia Barnes, Amanda Genever, Paul Bioengineering (Basel) Article Mesenchymal stem/stromal cells (MSCs) are typically characterised by their ability to differentiate into skeletal (osteogenic, chondrogenic and adipogenic) lineages. MSCs also appear to have additional non-stem cell functions in coordinating tissue morphogenesis and organising vascular networks through interactions with endothelial cells (ECs). However, suitable experimental models to examine these apparently unique MSC properties are lacking. Following previous work, we have developed our 3D in vitro co-culture models to enable us to track cellular self-organisation events in heterotypic cell spheroids combining ECs, MSCs and their differentiated progeny. In these systems, MSCs, but not related fibroblastic cell types, promote the assembly of ECs into interconnected networks through intrinsic mechanisms, dependent on the relative abundance of MSC and EC numbers. Perturbation of endogenous platelet-derived growth factor (PDGF) signalling significantly increased EC network length, width and branching. When MSCs were pre-differentiated towards an osteogenic or chondrogenic lineage and co-cultured as mixed 3D spheroids, they segregated into polarised osseous and chondral regions. In the presence of ECs, the pre-differentiated MSCs redistributed to form a central mixed cell core with an outer osseous layer. Our findings demonstrate the intrinsic self-organising properties of MSCs, which may broaden their use in regenerative medicine and advance current approaches. MDPI 2018-10-26 /pmc/articles/PMC6315484/ /pubmed/30373192 http://dx.doi.org/10.3390/bioengineering5040092 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Marshall, Julia
Barnes, Amanda
Genever, Paul
Analysis of the Intrinsic Self-Organising Properties of Mesenchymal Stromal Cells in Three-Dimensional Co-Culture Models with Endothelial Cells
title Analysis of the Intrinsic Self-Organising Properties of Mesenchymal Stromal Cells in Three-Dimensional Co-Culture Models with Endothelial Cells
title_full Analysis of the Intrinsic Self-Organising Properties of Mesenchymal Stromal Cells in Three-Dimensional Co-Culture Models with Endothelial Cells
title_fullStr Analysis of the Intrinsic Self-Organising Properties of Mesenchymal Stromal Cells in Three-Dimensional Co-Culture Models with Endothelial Cells
title_full_unstemmed Analysis of the Intrinsic Self-Organising Properties of Mesenchymal Stromal Cells in Three-Dimensional Co-Culture Models with Endothelial Cells
title_short Analysis of the Intrinsic Self-Organising Properties of Mesenchymal Stromal Cells in Three-Dimensional Co-Culture Models with Endothelial Cells
title_sort analysis of the intrinsic self-organising properties of mesenchymal stromal cells in three-dimensional co-culture models with endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315484/
https://www.ncbi.nlm.nih.gov/pubmed/30373192
http://dx.doi.org/10.3390/bioengineering5040092
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