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

Thomas P. Kraehenbuehl, Prisca Zammaretti, André J. Van der Vlies, Ronald G. Schoenmakers, Matthias P. Lutolf, Marisa E. Jaconi, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

211 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2757-2766
Number of pages10
JournalBiomaterials
Volume29
Issue number18
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Fingerprint

Artificial Cells
Ethylene Glycol
Hydrogel
Matrix Metalloproteinases
Hydrogels
Polyethylene glycols
Embryoid Bodies
Extracellular Matrix
Cells
Elasticity
Modulation
Suspensions
Embryonal Carcinoma
Embryonal Carcinoma Stem Cells
Myosin Heavy Chains
Tissue Engineering
Tissue
Integrins
Transcription factors
Ligation

Keywords

  • Biomimetic hydrogel
  • Cardiac tissue engineering
  • Extracellular matrix
  • P19 embryonal carcinoma cells
  • Poly(ethylene glycol)
  • Stem cells

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

Kraehenbuehl, T. P., Zammaretti, P., Van der Vlies, A. J., Schoenmakers, R. G., Lutolf, M. P., Jaconi, M. E., & Hubbell, J. A. (2008). Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: Systematic modulation of a synthetic cell-responsive PEG-hydrogel. Biomaterials, 29(18), 2757-2766. https://doi.org/10.1016/j.biomaterials.2008.03.016

Three-dimensional extracellular matrix-directed cardioprogenitor differentiation : Systematic modulation of a synthetic cell-responsive PEG-hydrogel. / Kraehenbuehl, Thomas P.; Zammaretti, Prisca; Van der Vlies, André J.; Schoenmakers, Ronald G.; Lutolf, Matthias P.; Jaconi, Marisa E.; Hubbell, Jeffrey A.

In: Biomaterials, Vol. 29, No. 18, 01.06.2008, p. 2757-2766.

Research output: Contribution to journalArticle

Kraehenbuehl, TP, Zammaretti, P, Van der Vlies, AJ, Schoenmakers, RG, Lutolf, MP, Jaconi, ME & Hubbell, JA 2008, 'Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: Systematic modulation of a synthetic cell-responsive PEG-hydrogel', Biomaterials, vol. 29, no. 18, pp. 2757-2766. https://doi.org/10.1016/j.biomaterials.2008.03.016
Kraehenbuehl, Thomas P. ; Zammaretti, Prisca ; Van der Vlies, André J. ; Schoenmakers, Ronald G. ; Lutolf, Matthias P. ; Jaconi, Marisa E. ; Hubbell, Jeffrey A. / Three-dimensional extracellular matrix-directed cardioprogenitor differentiation : Systematic modulation of a synthetic cell-responsive PEG-hydrogel. In: Biomaterials. 2008 ; Vol. 29, No. 18. pp. 2757-2766.
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