Projects

In previous studies^* we have demonstrated that human CD34⁺ cells are able to induce neovascularization. A property, which makes this specific cell attractive for therapeutic intervention after an ischemic insult, such as a myocardial infarction. However, the mechanism by which these cells contribute to neovascularization remains to be elucidated. Incorporation of differentiated CD34⁺ in the neovasculature has been described, whereas others attribute a paracrine function to these cells.

We investigate the mechanisms that govern CD34⁺ induced neovascularization, and the role that CD34⁺ cells play in the recruitment of inflammatory cells. Moreover, we are studying novel mechanisms for delivery of these cells for regenerative medicine purposes e.g. smart biomaterials that may be applied in the myocardial wall after myocardial infarction.

^* E.R. Popa et al. JMCC 2006, BWA vd Strate et al. JMCC 2007

The development of artificial cardiac tissue that could replace affected heart tissue after a myocardial infarct is one of the research topics in our group. Large myocardial constructs demand adequate oxygen and nutrient supply via capillaries by forming the wall of the capillaries as well as by secreting factors that directly may influence survival, differentiation and contractions of cardiomyocytes. We focus on unraveling the cellular interactions between cardiomyocytes and endothelial precursor cells in order to develop electrophysiological competent cardiac tissue constructs. To this end, the effects of e.g. biomaterials and inflammatory responses on interactions between cardiomyocytes and endothelial precursor cells will be investigated.

This research is supported by a grant from the Dutch Platform for Tissue Engineering (DPTE)

Vascular Tissue Engineering aims at generating an artificial small-diameter replacement blood vessel for use in amongst others bypass surgery. Ideally, this replacement vessel would comprise of a degradable biomaterial, and autologous endothelial and smooth muscle cells. The outer layer of biomaterial and smooth muscle cells provides the replacement vessel with mechanical strength and elasticity to withstand forces generated by blood flow, while the inner endothelial cell layer provides an antithrombogenic surface. The current project aims at identifying circulating progenitors which can be differentiated into endothelial- or smooth muscle cells and to unravel the molecular mechanisms that drive their respective differentiation fates.

We have identified several circulating cell types which can be differentiated into endothelial cells in vitro. By combining these cells, we were able to speed up differentiation whilst maintaining proliferative capacity, or self-renewal of these endothelial cells. Furthermore, we found that endothelial (progenitor) cells have the ability to transdifferentiate into smooth muscle cells, opening new opportunities for progenitor-cell based vascular tissue engineering.

Supported by BMSA

Krenning et al. Biomaterials 2007

EPC have been shown to have beneficial effects in cardiovascular diseases by incorporation into sites of endothelial damage and improvement of vascularization of ischemic tissues. However, little is known about the differentiation and functionality of these cells in situ.

We have shown that endothelial cells are capable of endothelial-to-mesenchymal transdifferentiation, and whilst this process is physiological during embryogenesis (e.g. heart valve development), we hypothesize that this phenomenon also contributes to the pathophysiology of atherosclerosis.

E(P)C are exposed to a plethora of stimuli (e.g. growth factors, inflammatory mediators, metabolic products) which may negatively influence the differentiation of EPC and endothelial cell function. In this project, we aim at unraveling the effects of these stimuli on E(P)C differentiation, plasticity and functionality in vitro and in vivo.

This research is financially supported by GUIDE