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A better understanding of cardiac fibrosis. That was the clear goal of the PhD project of Tom Bracco Gartner. Tom developed new models for cardiac fibrosis. He demonstrated their potential for therapy testing and studied the effect of stretching on heart cells. He defended his thesis on May 6th.  

The need for better models 

Scarring of heart tissue, also known as cardiac fibrosis, is an important histological characteristic of heart failure. This can have various causes, the most common being a myocardial infarction, and affects the functioning of the heart. To date, there are no effective therapies specifically targeting cardiac fibrosis. This is at least partly due to ineffective drug development and an incomplete understanding of cardiac fibrosis. A lack of representative models of cardiac fibrosis hampered progress in both areas. Tom’s efforts took us a step closer to understanding and addressing cardiac fibrosis.  

Best of both worlds 

His PhD project was a collaborative project between the Regenerative Medicine Center Utrecht and Eindhoven University of Technology. “I spent most of my time here in Utrecht because here the facilities to culture 3D cardiac tissue are well-developed. But I needed the technological knowledge from Eindhoven for building the new organ-on-a-chip models. That meant that in the beginning that I was moving with either my cells to Eindhoven or with the prototypes of the organ-on-a-chip models to Utrecht.” 

From 2D to 3D culture 

Previously, 2D culturing of cardiac fibroblasts, the cells that are activated in cardiac fibrosis, were the only model for cardiac fibrosis. But this doesn’t represent the three-dimensional, elastic and moving environment of the human heart tissue. The conventional culturing techniques in cell culture flasks automatically lead to the activation of the cardiac fibroblasts, a hallmark of cardiac fibrosis, making it complicated to study this process. Therefore, Tom used a 3D culture of cardiac fibroblasts, using a hydrogel to mimic the elastic environment of the heart. When heart muscle cells were also included, this 3D heart tissue was able to contract just like the human heart does. This model could then be used to test and understand potential therapies to target cardiac fibrosis. 

The effect of stretch 

Tom also worked on understanding the effect of stretching on heart cells, something that was still under debate. By developing a second model, a so-called organ-on-a-chip model, he was able to test the effect of different forces on the heart cells. With that model, they were able to show that the normal stretching forces of the heart counter cardiac scarring. Thereby highlighting the importance of taking these forces into account when studying fibrosis.  

What’s next? 

Tom is currently completing his residency in Cardiothoracic Surgery at the UMC Utrecht. Tom hopes to continue as a cardiac surgeon in the field of heart failure. His PhD research is quite fundamental for someone who aimed to become a heart surgeon. Tom: “I had actually just decided not to do a PhD at all, because I didn’t really like full-time epidemiological research. But then this project came along, containing much more practical research. That suited me much better. The downside was that it was still far from the patient.'   

Will he ever return to the lab? “I find it incredibly interesting, but unfortunately, this kind of research is hard to combine with working as a heart surgeon. Still, perhaps in the future I can use my knowledge from both fields to support researchers to translate their research to the clinic. I’d love to explore opportunities for that kind of collaboration,” concludes Tom.