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

Paper ID Volume ID Publish Year Pages File Format Full-Text
9862 650 2008 10 PDF Available
Title
Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: Systematic modulation of a synthetic cell-responsive PEG-hydrogel
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 = 4036 ± 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 (α5β1, αvβ3) 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
Extracellular matrix; Biomimetic hydrogel; Poly(ethylene glycol); Cardiac tissue engineering; P19 embryonal carcinoma cells; Stem cells
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Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: Systematic modulation of a synthetic cell-responsive PEG-hydrogel
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 29, Issue 18, June 2008, Pages 2757–2766
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us