Optimizing delivery of target genes to develop biological pacemakers
One of the great limitations of electronic pacemakers is the inadequate response to adrenergic modulation. Our aim is to improve rate responsiveness by developing an effective platform for long-term cardiac delivery of target genes that are involved in the embryonic development of the cardiac conduction system. For delivery of transgenes, we are exploring the in vivo use of adeno-associated viral vectors (AAV), lentiviruses (LV) as well as ex vivo modification of human cardiomyocyte progenitor cells (hCMPCs).
EMT increases the therapeutic potential of epicardial cell transplantation after MI
Previous research has shown that cardiac progenitor-cell based therapies after myocardial infarction (MI), including transplantation of spindle-shaped epicardial-derived cells (sEPDCs), can preserve cardiac function and increase vascularization. sEPDCs have already undergone epithelial-to-mesenchymal transition (EMT) prior to transplantation. We recently developed a protocol for culturing the epithelial-like cobblestone (c)EPDCs. As cEPDCs have not yet undergone EMT, we reasoned that they are more plastic and less restricted to differentiate into a certain mesenchymal cell type than sEPDCs. Our aim is to compare therapeutic potential and the paracrine profile of either cell type.
I started my scientific career as a student Biomedical Sciences at the Utrecht University. During my second internship in the laboratory of experimental cardiology of professor Sluijter in the UMC Utrecht, I became interested in the therapeutical potential of cardiac stem cells after myocardial damage. As such I started my PhD in the group of professor Goumans in the LUMC. Currently, I’m in the fourth year of my PhD project, that focuses on (stem)cells and viruses as a delivery method for different cardiac diseases; e.g. paracrine factors after myocardial infarction or gene delivery to create a biological pacemaker.
ORCID ID: 0000-0002-4398-2572
• Human Cardiomyocyte Progenitor Cells in Co-culture with Rat Cardiomyocytes Form a Pro-arrhythmic Substrate: Evidence for Two Different Arrhythmogenic Mechanisms.
Smit NW,† Cócera Ortega L,† Végh AMD, Meijborg VMF, Smits AM, Klerk M, Tijsen AJM, Tan HL, Goumans MJTH, Boink GJJ, and Coronel R.
Front Physiol. 2017. 8:797
• Part and Parcel of the Cardiac Autonomic Nerve System: Unravelling Its Cellular Building Blocks during Development.
Végh AMD, Duim SN, Smits AM, Poelmann RE, Ten Harkel ADJ, DeRuiter MC, Goumans MJTH, and Jongbloed MRM.
J Cardiovasc Dev Dis. 2016. 3(3);28:1-29
• Cardiac Stem Cell Treatment in Myocardial Infarction: A Systematic Review and Meta-Analysis of Preclinical Studies.
Zwetsloot PPM,† Végh AMD,† Jansen of Lorkeers SJ, Van Hout GPJ, Currie GL, Sena ES, Gremmels H, Buikema JW, Goumans MJTH, Macleod MR, Doevendans PA, Chamuleau SAJ, and Sluijter JPG.
Circ Res. 2016. 15;118(8):1223-32.
Groups: Cardiovascular Cell Biology