Frontiers in Cardiovascular Medicine (Apr 2019)
Anti-fibrotic Effects of Cardiac Progenitor Cells in a 3D-Model of Human Cardiac Fibrosis
- Tom C. L. Bracco Gartner,
- Tom C. L. Bracco Gartner,
- Tom C. L. Bracco Gartner,
- Tom C. L. Bracco Gartner,
- Janine C. Deddens,
- Janine C. Deddens,
- Emma A. Mol,
- Emma A. Mol,
- Marina Magin Ferrer,
- Linda W. van Laake,
- Linda W. van Laake,
- Linda W. van Laake,
- Carlijn V. C. Bouten,
- Ali Khademhosseini,
- Pieter A. Doevendans,
- Pieter A. Doevendans,
- Pieter A. Doevendans,
- Pieter A. Doevendans,
- Pieter A. Doevendans,
- Pieter A. Doevendans,
- Willem J. L. Suyker,
- Willem J. L. Suyker,
- Willem J. L. Suyker,
- Joost P. G. Sluijter,
- Joost P. G. Sluijter,
- Joost P. G. Sluijter,
- Jesper Hjortnaes,
- Jesper Hjortnaes,
- Jesper Hjortnaes
Affiliations
- Tom C. L. Bracco Gartner
- Division Heart, and Lungs, Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, Netherlands
- Tom C. L. Bracco Gartner
- Laboratory of Experimental Cardiology, Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
- Tom C. L. Bracco Gartner
- Soft Tissue Engineering and Mechanobiology, Department of Biomedical Technology, Eindhoven University of Technology, Eindhoven, Netherlands
- Tom C. L. Bracco Gartner
- Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, Netherlands
- Janine C. Deddens
- Laboratory of Experimental Cardiology, Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
- Janine C. Deddens
- Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
- Emma A. Mol
- Laboratory of Experimental Cardiology, Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
- Emma A. Mol
- Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
- Marina Magin Ferrer
- Laboratory of Experimental Cardiology, Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
- Linda W. van Laake
- Laboratory of Experimental Cardiology, Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
- Linda W. van Laake
- Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, Netherlands
- Linda W. van Laake
- Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
- Carlijn V. C. Bouten
- Soft Tissue Engineering and Mechanobiology, Department of Biomedical Technology, Eindhoven University of Technology, Eindhoven, Netherlands
- Ali Khademhosseini
- Department of Bioengineering, Department of Radiology, Department of Chemical and Biomolecular Engineering, Director of Center for Minimally Invasive Therapeutics (C-MIT), University of California, Los Angeles, Los Angeles, CA, United States
- Pieter A. Doevendans
- Laboratory of Experimental Cardiology, Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
- Pieter A. Doevendans
- Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, Netherlands
- Pieter A. Doevendans
- Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
- Pieter A. Doevendans
- Utrecht University, Utrecht, Netherlands
- Pieter A. Doevendans
- Netherlands Heart Institute, Utrecht, Netherlands
- Pieter A. Doevendans
- 0Central Military Hospital, Utrecht, Netherlands
- Willem J. L. Suyker
- Division Heart, and Lungs, Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, Netherlands
- Willem J. L. Suyker
- Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, Netherlands
- Willem J. L. Suyker
- Utrecht University, Utrecht, Netherlands
- Joost P. G. Sluijter
- Laboratory of Experimental Cardiology, Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
- Joost P. G. Sluijter
- Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, Netherlands
- Joost P. G. Sluijter
- Utrecht University, Utrecht, Netherlands
- Jesper Hjortnaes
- Division Heart, and Lungs, Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, Netherlands
- Jesper Hjortnaes
- Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, Netherlands
- Jesper Hjortnaes
- Utrecht University, Utrecht, Netherlands
- DOI
- https://doi.org/10.3389/fcvm.2019.00052
- Journal volume & issue
-
Vol. 6
Abstract
Cardiac fibroblasts play a key role in chronic heart failure. The conversion from cardiac fibroblast to myofibroblast as a result of cardiac injury, will lead to excessive matrix deposition and a perpetuation of pro-fibrotic signaling. Cardiac cell therapy for chronic heart failure may be able to target fibroblast behavior in a paracrine fashion. However, no reliable human fibrotic tissue model exists to evaluate this potential effect of cardiac cell therapy. Using a gelatin methacryloyl hydrogel and human fetal cardiac fibroblasts (hfCF), we created a 3D in vitro model of human cardiac fibrosis. This model was used to study the possibility to modulate cellular fibrotic responses. Our approach demonstrated paracrine inhibitory effects of cardiac progenitor cells (CPC) on both cardiac fibroblast activation and collagen synthesis in vitro and revealed that continuous cross-talk between hfCF and CPC seems to be indispensable for the observed anti-fibrotic effect.
Keywords
- cardiac fibrosis
- cardiac tissue engineering
- in vitro 3D models
- cardiac progenitor cells
- stem cell therapy
- extracellular vesicles