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Acta BiomaterialiaVolume 10, Issue 7, July 2014, Pages 3197-3208

Matrix-driven formation of mesenchymal stem cell-extracellular matrix microtissues on soft alginate hydrogels(Article)

  • aInstituto de Engenharia Biomédica (INEB), Rua do Campo Alegre, No. 823, 4150-180 Porto, Portugal
  • bFaculdade de Engenharia, Universidade Do Porto (FEUP), Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal
  • cCentro de Biologia Ambiental/Departamento de Biologia Animal, Faculdade de Ciências, Universidade de Lisboa (FCUL), Campo Grande s/n, 1749-016 Lisboa, Portugal
  • dInstituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade Do Porto, Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal

Abstract

Mesenchymal stem cells (MSCs) can be made to rearrange into microtissues in response to specific matrix cues, a process that depends on a balance between cell-matrix and cell-cell interactions. The effect of such cues, and especially their interplay, is still not fully understood, particularly in three-dimensional (3-D) systems. Here, the behaviour of human MSCs cultured within hydrogel matrices with tailored stiffness and composition was evaluated. MSC aggregation occurred only in more compliant matrices (G′ ≤ 120 Pa), when compared to stiffer ones, both in the presence and in the absence of matrix-bound arginine-glycine-aspartic acid cell-adhesion ligands (RGD; 0, 100 and 200 μM). Fibronectin assembly stabilized cell-cell contacts within aggregates, even in non-adhesive matrices. However, MSCs were able to substantially contract the artificial matrix only when RGD was present. Moreover, compliant matrices facilitated cell proliferation and provided an environment conducive for MSC osteogenic differentiation, even without RGD. Cell interactions with the original matrix became less important as time progressed, while the de novo-produced extracellular matrix became a more critical determinant of cell fate. These data provide further insights into the mechanisms by which MSCs sense their microenvironment to organize into tissues, and provide new clues to the design of cell-instructive 3-D matrices. © 2014 Published by Elsevier Ltd. on behalf of Acta Materialia Inc.

Author keywords

Cell aggregationCell tractionCell-matrix interactionsHydrogelsViscoelastic properties

Indexed keywords

EMTREE drug terms:alginic acidargininearginylglycylaspartic acidaspartic acidfibronectinglycineintegrin receptorligandalginic acidglucuronic acidhexuronic acidhydrogel
EMTREE medical terms:articlebone developmentcell adhesioncell aggregationcell communicationcell differentiationcell functioncell interactioncell proliferationcontrolled studydry massextracellular matrixhumanhuman cellhydrogelmesenchymal stem cellmicroenvironmentmolecular weightpriority journalprotein assemblyrigiditycell culturecell motioncytologyhydrogelmesenchymal stroma cellscanning electron microscopy
MeSH:AlginatesCell DifferentiationCell MovementCells, CulturedExtracellular MatrixGlucuronic AcidHexuronic AcidsHumansHydrogelsMesenchymal Stromal CellsMicroscopy, Electron, Scanning

Chemicals and CAS Registry Numbers:

alginic acid, 28961-37-7, 29894-36-8, 9005-32-7, 9005-38-3; arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; arginylglycylaspartic acid, 99896-85-2; aspartic acid, 56-84-8, 6899-03-2; fibronectin, 86088-83-7; glycine, 56-40-6, 6000-43-7, 6000-44-8; glucuronic acid, 36116-79-7, 576-37-4, 6556-12-3;

Alginates; alginic acid; Glucuronic Acid; Hexuronic Acids; Hydrogels

Funding details

Funding sponsor Funding number Acronym
Programa Operacional Temático Factores de CompetitividadeCOMPETE
Fundação para a Ciência e a Tecnologia
See opportunities
FCOMP-01-0124-FEDER-010915,PTDC/SAU-BEB/101235/2008
Fundação para a Ciência e a Tecnologia
See opportunities		Pest-C/SAU/LA0002/2011

  • 1

    This work was financed by FEDER funds through the Programa Operacional Factores de Competitividade (COMPETE) and by Portuguese funds through Fundação para a Ciência e a Tecnologia (FCT), in the framework of the projects Pest-C/SAU/LA0002/2011 and BIOMATRIX (PTDC/SAU-BEB/101235/2008 and FCOMP-01-0124-FEDER-010915). F.R.M. acknowledges INL-International Iberian Nanotechnology Laboratory for her PhD scholarship. K.B.F. acknowledges her PhD scholarship from FCT-POPH (SFRH/BD/30057/2006). C.B. has a research position funded by FCT-POPH-FSE (Ciência 2008). The authors are grateful to Sara Neves and David Gomes from INEB, for the help in the rheological and histological analyses, respectively. Appendix A

  • ISSN: 17427061
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.actbio.2014.02.049
  • PubMed ID: 24607421
  • Document Type: Article
  • Publisher: Elsevier Ltd

  Barrias, C.C.; Instituto de Engenharia Biomédica (INEB), Rua do Campo Alegre, No. 823, Portugal;
© Copyright 2014 Elsevier B.V., All rights reserved.

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