An interview with Prof. Stefano Severi

 

We met Stefano Severi – Assistant Professor of Biomedical Engineering department of Electronics, Computer Science and Systems of the University of Bologna, Italy – who created a computational model which is at the core of STrhiPS: a web-based tool that helps perform in silico trials on populations of hiPS (human induced Pluripotent Stem) cells. After graduating in Electronic Engineering in 1993Severi received a PhD in Bioengineering in 1998. He has written over 200 papers, 80 of which published in peer reviewed international journals with Impact Factor. Since 1996, he has participated to 31 funded research projects. He serves as a reviewer for several peer-reviewed international journals and for the Italian Ministry of Research. 

STrhiPS is a revolutionary tool to conduct in silico safety trials on a population of hiPS cells, for 7 ion channels and at different concentrations. “The idea of a computational model of a stem cell derived cardiomyocyte originated several years ago, discussing with a colleague, the electrophysiologist Elisabetta Cerbai”, said Stefano Severi. “She proposed me to work on computational modeling of this peculiar type of cells. I focused on the induced pluripotent stem cell derived cardiomyocytes: we believed that having a computational tool to investigate the physiology of these specific cells, would help us understand their functioning. 

This idea was developed in collaboration with Michelangelo Paci, who was a PhD student in Severi’s lab at that time. “We worked together on the hiPSC derived cardiomyocyte model, leveraging our past experience on different cardiac cell types”, recalls Severi“We focused on a comprehensive characterization of this kind of cells through voltage clamp experiments, which had been done by the Craig January’lab in the US, using both a manual tuning approach and optimization techniques to find the final parameter set of the model. 

The most important problem solved by STrhiPS is the possibility to test the effect of multi-channel blocker compounds on a very large population of virtual cells. The physiological variability peculiar of these cells can be included into the analysis and this can be done without having to worry about the implementation, the hardware requirements and so on. 

What is so unique in this model?

One of the main advantages of using our computational modelis that the parameters of each ionic current can be changed and the effect on the whole cell behavior can be predicted easily also by separating the effects of each intervention, which is not easily feasible in real experiments. What makes our model unique is that for a long time, it has been the only model of this kind of stem cells derived cardiomyocytes. So it has been tested and verified by several scientists all over the world. And it has been proven to reproduce very different behaviors of the cells and also some pathological states and the drug effect of several channel blockers. So, I think it is the most reliable, robust computational model available of these cells. 

 

Prof. Severi started working with usafter he was contacted with the proposal of implementing this model onto our web platform. He immediately found very relevant the possibility of making the model available for fast application in the real world. “Academic scientists are offered a fast translational path, so that the model can be used by people or companies interested in testing new compounds on the electrophysiology of the cells, also if they have little experience with simulation”. 

Last thing we want to ask is: how can simulation be a game changer for the healthcare industry today? “I think that simulation of physiological systems starting from cells, whole organs or even the entire organism of a virtual patient has reached such a level of reliability that is going to completely change the preclinical phase in the design and also in the safety and efficacy assessment of medical devices and drugs. And this will make it definitely less costly and shorten the time to market of new products. Last but not least, simulation can reduce the use of animal testing for this phase. I think the process has already started, but we are only at the beginning. 

You can watch our video interview to Prof. Stefano Severi here: 

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