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Analysis of the intrinsic self-organising properties of mesenchymal stromal cells in three-dimensional co-culture models with endothelial cells

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JournalBioengineering
DateAccepted/In press - 24 Oct 2018
DatePublished (current) - 26 Oct 2018
Issue number4
Volume5
Number of pages13
Original languageEnglish

Abstract

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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© 2018 by the authors. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

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