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Title

Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: systematic modulation of a synthetic cell-responsive PEG-hydrogel

Authors
Kraehenbuehl, T. P.
Zammaretti, Prisca
Van der Vlies, A. J.
Schoenmakers, R. G.
Lutolf, M. P.
Hubbell, J. A.
Published in Biomaterials. 2008, vol. 29, no. 18, p. 2757-2766
Abstract We show that synthetic three-dimensional (3D) matrix metalloproteinase (MMP)-sensitive poly(ethylene glycol) (PEG)-based hydrogels can direct differentiation of pluripotent cardioprogenitors, using P19 embryonal carcinoma (EC) cells as a model, along a cardiac lineage in vitro. In order to systematically probe 3D matrix effects on P19 EC differentiation, matrix elasticity, MMP-sensitivity and the concentration of a matrix-bound RGDSP peptide were modulated. Soft matrices (E=322+/-64.2 Pa, stoichiometric ratio: 0.8), mimicking the elasticity of embryonic cardiac tissue, increased the fraction of cells expressing the early cardiac transcription factor Nkx2.5 around 2-fold compared to embryoid bodies (EB) in suspension. In contrast, stiffer matrices (E=4,036+/-419.6 Pa, stoichiometric ratio: 1.2) decreased the number of Nkx2.5-positive cells significantly. Further indicators of cardiac maturation were promoted by ligation of integrins relevant in early cardiac development (alpha(5)beta(1,) alpha(v)beta(3)) by the RGDSP ligand in combination with the MMP-sensitivity of the matrix, with a 6-fold increased amount of myosin heavy chain (MHC)-positive cells as compared to EB in suspension. This precisely controlled 3D culture system thus may serve as a potential alternative to natural matrices for engineering cardiac tissue structures for cell culture and potentially therapeutic applications.
Keywords AnimalsCell Differentiation/drug effects/ physiologyCell Line, TumorCell Proliferation/drug effectsExtracellular Matrix/chemistry/ physiologyFlow CytometryHydrogel/chemical synthesis/chemistryImmunohistochemistryMuscle, Skeletal/cytology/drug effects/metabolismPolyethylene Glycols/ chemistryReverse Transcriptase Polymerase Chain ReactionTissue Engineering/ methods
Identifiers
PMID: 18396331
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Structures
Research group Mécanismes de différentiation cellulaire des cellules cardiaques (536)
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KRAEHENBUEHL, T. P. et al. Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: systematic modulation of a synthetic cell-responsive PEG-hydrogel. In: Biomaterials, 2008, vol. 29, n° 18, p. 2757-2766. https://archive-ouverte.unige.ch/unige:11383

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Deposited on : 2010-08-27

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