By Hamideh Emrani
It always feels amazing to find a solution to a problem or challenge. I think this huge sense of accomplishment is what drives many people in the research community. During my academic career, I have come across some remarkable scientists and researchers who thrive on problem solving. I find it intriguing to hear how these people come up with solutions, and what process they go through. So, with that in mind, I am beginning a series of interviews with leaders and experts in the field of Biomaterials.
I am starting my series with Professor Craig A. Simmons, my trusted go to person and mentor whenever I needed advice regarding my research career.
Professor Simmons is the Canada Research Chair in Mechanobiology at the University of Toronto. I encourage you to read his bio and list of awards here.
Cardiovascular diseases are the leading causes of death worldwide. Many researchers are trying to find solutions to prevent and treat the various different classes that cause heart problems. Professor Simmons leads a talented research group that investigates the processes by which biomechanical forces regulate tissue regeneration and disease in the heart valve. They also study applications of stem cells in the regeneration of heart tissue and create novel biomedical microdevices to model normal and diseased tissues.
Here’s my interview with Prof. Simmons.
Your lab works on cellular mechanobiology in stem cells and heart tissue. What attracted you to this subject and what is the impact of researching this aspect of cells?
In my group, we are interested in determining how mechanical forces regulate cells to either maintain a healthy valve or cause dysfunction. The heart valve contains stem cells that become dysregulated and create bone and fibrotic tissue in the valve, which prevents it from opening and closing properly. This is a very common disease with no medical solution. The only solution available right now is to wait until the valve completely stops functioning and replace it with a prosthetic.
There is good evidence that mechanical forces impact the progression of heart valve disease. For instance, people with high blood pressure have a greater chance of developing heart valve disease. We study the role of mechanical forces in heart valve disease in vitro by putting valve stem cells on biomaterials with defined properties and subjecting them to physiological forces. This way we observe how the valve cells’ matrix and mechanical environment regulate their function. We then follow up these in vitro studies with animal studies in vivo. We are also seeking alternative solutions to replace defective valves by engineering replacement heart valve tissue from stem cells and biomaterials.
Can you explain a bit more about the type of projects that your group works on these days?
In addition to studying heart valve disease and treatments, our group develops microfluidic platforms. These systems allow us to study how cells respond to mechanical forces, by controlling the mechanical environment very precisely and doing so with higher throughput than is normally used, enabling us to perform more experiments.
We have generated microfluidic platforms that contain arrays of microtissues. The benefit of these platforms compared to traditional culture methods is that they mimic the 3D environment and function of the tissue more accurately. For example, we have created vascularized microtissues within microplates and can use these to model cardiovascular tissues or pretty much any tissue that has a blood vessel in it. We expect this to be a useful technology to improve drug screening and toxicology testing.
Does the same concept apply to “Organ-on-a-Chip”?
Yes. Most organs contain vessels through which blood flows. The actual physical force of the blood on the blood vessel cells is missing in most tissue culture platforms. We have incorporated this important component in our tissue culture systems, as blood flow influences how cells respond to drugs and how a drug is delivered to the cells and tissue. We are currently working to commercialize and translate some of these technologies through collaborations with the Centre for Commercialization of Regenerative Medicine.
What do you see as a main challenge in your field of work/research?
In the biomicrofluidics field, the main challenge is to make the technologies and tools that we invent in the lab robust and easy-to-use so that end users, like biologists and clinicians, will adopt them and use them routinely. Fortunately, we are making good progress to that end.
From the perspective of heart valve disease, there are two challenges. First, the underlying mechanisms that lead to heart valve failure are still not well understood and the treatment strategies attempted to date have been ineffective. Better success may come from identifying early disease targets and being able to diagnose valve disease earlier and more definitively through imaging techniques and biomarkers. The second challenge is that currently there is no perfect heart valve replacement. This is especially problematic for children with valve defects, as they grow and their valves need to grow with them to avoid multiple re-operations during their lifetime. We are tackling both of these challenges and are optimistic that solutions for heart valve disease will result from our work.
Hamideh Emrani is a freelance communicator specializing in scientific communications. She earned her B.Sc. in Cell and Molecular Biology at UC Berkeley and finished her M.Sc. at the University of Toronto (U of T), Faculty of Dentistry, the Bone Interface Lab. She was an intern at the Carnegie Institute at Stanford University, honours research student at UC Berkeley and has won awards for best podium and best poster presentations at the Faculty of Dentistry and IBBME at U of T. She is passionate about science and loves to talk and write about it. You can follow Hamideh on Twitter at @HamidehEmrani.