Dr. Anke Smits

Dr. Smits obtained her PhD at the department of exp. Cardiology at the UMCU. Here, she investigated cardiac-tissue derived progenitor cells and their ability to become cardiac cell types in vitro and in vivo. As a post-doc, she joined the cardiovascular cell biology group in the LUMC to to continue this research. A Rubicon fellowship allowed her to join the lab of Prof. Riley at University College London/ Oxford University to learn more about the potential of epicardial-derived cells in cardiac. She returned to the LUMC in 2013 and continued to study cardiac (progenitor) cells and their endogenous repair capacity, funded by a NWO-VENI, and a LUMC Research fellowship. In 2017, she was awarded a Dutch Heart foundation- Dekker grant to expand her research group as an assistant professor focusing on the epicardium and local application of stimulants. Additionally, she is a member of the DEC (Animal ethichs committee), served as a board member of the European Society of Cardiology’s Scientists of Tomorrow, and is currently on the board of the Dutch Young@Heart to help secure the future of young cardiovascular scientists. As a cardiovascular cell biologist, Dr. Smits is interested in cells that can contribute to repair of the injured heart. She focuses on cell-based therapies, and on stimulation of endogenous cells with reparative capacity, with a specific interest in the epicardium. Cell-based therapy includes the delivery of cells or cell-derived products that can contribute to repair of the injured myocardium via e.g. direct differentiation, paracrine mechanisms, or matrix remodelling. Dr. Smits focuses on the identification of an optimal cell (product) to stimulate reparative capacity of the heart. To this end, she combines cell and tissue culture methods with pre-clinical models for e.g. myocardial infarction, and state-of-the-art small animal imaging modules.

Most recent publications

Editorial: Novel strategies to repair the infarcted heart, volume II
Smits AM, Bollini S and Gladka MM
Editorial: Straight from the heart: Novel insights and future perspectives for cardiac repair
Bollini S, Gladka MM and Smits AM
Acute myocardial infarction induces remodeling of the murine superior cervical ganglia and the carotid body
Ge Y, van Roon L, van Gils JM, Geestman T, van Munsteren CJ, Smits AM, Goumans MJTH, DeRuiter MC and Jongbloed MRM
A role for cardiac sympathetic hyperinnervation in arrhythmogenesis after myocardial infarction (MI) has increasingly been recognized. In humans and mice, the heart receives cervical as well as thoracic sympathetic contributions. In mice, superior cervical ganglia (SCG) have been shown to contribute significantly to myocardial sympathetic innervation of the left ventricular anterior wall. Of interest, the SCG is situated adjacent to the carotid body (CB), a small organ involved in oxygen and metabolic sensing. We investigated the remodeling of murine SCG and CB over time after MI. Murine SCG were isolated from control mice, as well as 24 h, 3 days, 7 days and 6 weeks after MI. SCG and CBs were stained for the autonomic nervous system markers β3-tubulin, tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT), as well as for the neurotrophic factors brain derived neurotropic factor (BDNF), nerve growth factor (NGF) and their tyrosine receptor kinase (pan TRK). Results show that after MI a significant increase in neuron size occurs, especially in the region bordering the CB. Co-expression of TH and ChAT is observed in SCG neuronal cells, but not in the CB. After MI, a significant decrease in ChAT intensity occurs, which negatively correlated with the increased cell size. In addition, an increase of BDNF and NGF at protein and mRNA levels was observed in both the CB and SCG. This upregulation of neurotropic factors coincides with the upregulation of their receptor within the SCG. These findings were concomitant with an increase in GAP43 expression in the SCG, which is known to contribute to axonal outgrowth and elongation. In conclusion, neuronal remodeling toward an increased adrenergic phenotype occurs in the SCG, which is possibly mediated by the CB and might contribute to pathological hyperinnervation after MI.
Activin A and ALK4 Identified as Novel Regulators of Epithelial to Mesenchymal Transition (EMT) in Human Epicardial Cells
Dronkers E, van Herwaarden T, van Brakel TJ, Sanchez-Duffhues G, Goumans MJ and Smits AM
The epicardium, the mesothelial layer covering the heart, is a crucial cell source for cardiac development and repair. It provides cells and biochemical signals to the heart to facilitate vascularization and myocardial growth. An essential element of epicardial behavior is epicardial epithelial to mesenchymal transition (epiMT), which is the initial step for epicardial cells to become motile and invade the myocardium. To identify targets to optimize epicardium-driven repair of the heart, it is vital to understand which pathways are involved in the regulation of epiMT. Therefore, we established a cell culture model for human primary adult and fetal epiMT, which allows for parallel testing of inhibitors and stimulants of specific pathways. Using this approach, we reveal Activin A and ALK4 signaling as novel regulators of epiMT, independent of the commonly accepted EMT inducer TGFβ. Importantly, Activin A was able to induce epicardial invasion in cultured embryonic mouse hearts. Our results identify Activin A/ALK4 signaling as a modulator of epicardial plasticity which may be exploitable in cardiac regenerative medicine.
Single-cell analysis of human fetal epicardium reveals its cellular composition and identifies CRIP1 as a modulator of EMT
Streef TJ, Groeneveld EJ, van Herwaarden T, Hjortnaes J, Goumans MJ and Smits AM
The epicardium plays an essential role in cardiogenesis by providing cardiac cell types and paracrine cues to the developing myocardium. The human adult epicardium is quiescent, but recapitulation of developmental features may contribute to adult cardiac repair. The cell fate of epicardial cells is proposed to be determined by the developmental persistence of specific subpopulations. Reports on this epicardial heterogeneity have been inconsistent, and data regarding the human developing epicardium are scarce. Here we specifically isolated human fetal epicardium and used single-cell RNA sequencing to define its composition and to identify regulators of developmental processes. Few specific subpopulations were observed, but a clear distinction between epithelial and mesenchymal cells was present, resulting in novel population-specific markers. Additionally, we identified CRIP1 as a previously unknown regulator involved in epicardial epithelial-to-mesenchymal transition. Overall, our human fetal epicardial cell-enriched dataset provides an excellent platform to study the developing epicardium in great detail.