Why is cell therapy for cardiac regeneration still a myth? A 3D cardiac hydrogel model system to unravel the myth

Requirements

For this project, I’m looking for a very motivated and enthusiastic student, who has affinity with cell culture and tissue engineering. As a student you should have great enthusiasm for the subject and skills in systematic analyzing and investigating.

Description

Cell therapy as treatment for treatment of cardiac disease has been extensively studied in both animal studies and clinical trials. In general, cardiac cell therapy provides mixed results from mixed cells. Only minor increase in cardiac function is reported due to low cell retention and differentiation potential is limited. The positive effects that are observed on the short term are mainly ascribed to paracrine signaling. So the numerous trials have not reached a conclusion if cell therapy for cardiac regeneration is myth or reality.

As part of the project of the Dutch Heart Foundation “Combining myocardial unloading and cardiac progenitor cells: the next step in endogenous cardiac repair”, we would like to gain more insight in why cell therapy with the use of human cardiac progenitor cells (CPCs) fails to regenerate the heart, although these cells are a promising cell source. With the use of an engineered in vitro cardiac model system with anisotropic (aligned) and isotropic (disorganized) matrix fibers, the influence of tissue organization on the contribution of CPCs to cardiac remodeling will be investigated. The overall goal of the Heart Foundation project is to test whether unloading of the heart with a ventricular assist device, is beneficial for cardiac regeneration, since unloading will induce tissue remodeling towards a favorable environment for CPCs to reverse fibrotic tissue formation and contribute to the formation of functional “healthy” heart tissue.

In this Master Thesis Project, the goal is to develop a method to create a 3D hydrogel culture system with both anisotropic and isotropic matrix orientation, as described by Van Spreeuwel et al 2014. This 3D culture system will be used to investigate CPC behavior related to differentiation and matrix remodeling potential. In first instant, we will start by creating 3D culture systems with commercial hydrogels. When successful, the final goal is to create human ECM hydrogels combined with synthetic biomaterials.