Photo courtesy of University of Toronto

In the fight against heart disease, the world's leading cause of death, enabling researchers to learn more about the efficacy and toxicity of drugs before going into human trials saves money and lives.

"Cardiac toxicity is a big problem, and a reason why roughly a third of drugs don't make it through trials," says Dr. Milica Radisic, University of Toronto (U of T) Professor and Canada Research Chair. Radisic's U of T lab has developed breakthrough technology called AngioChip (often referred to as "heart-on-a-chip," "person-on-a-chip," and "organ-on-a chip") that rivals the work performed by similar labs elsewhere in the world. The difference is that her team uses polymers and isolated cells to make vasculature that is fully permeable to both small and large molecules.

Person-on-a-chip technology developed at U of T creates living, beating heart tissue inside the lab

Take a look at the living heart tissue that contains blood vessels and beats rhythmically, just like a real heart.

Disclaimer: this video links to a third party source. This video is not hosted by the Government of Ontario and there may not be a French version or transcripts available.

U of T's expertise in medicine and engineering key to breakthrough

"Traditionally, people could only do this using devices that squish the cells between sheets of silicon and glass, and using pumps and vacuum lines to deliver blood to the tissue," says Radisic. "Our platform is very user-friendly, considering industry doesn't like to use such pumps and vacuums." Radisic's lab developed the platform with the help of Boyang Zhang, a chemical engineer, who joined the team in 2010.

Ontario is definitely a top 5 centre. We have top clinicians, scientists and engineers all in the same place – and that is unique,

– Dr. Milica Radisic, Professor, University of Toronto and Canada Research Chair

Dr. Milica Radisic, University of Toronto
Dr. Milica Radisic, University of Toronto
Photo courtesy of University of Toronto

"Our goal was to make artificial tissues, but within these tissues there is a critical component, the blood vessel network, and creating that network has been a major challenge in this field," say Zhang. His solution was to apply Microfluidics, a technology used to manipulate and control fluids within micro networks, to develop a more robust system for growing organ tissue. "We tweaked the technique to adopt the fabrication of a bio material – a synthetic polymer to make up the scaffold. The original material used was not biodegradable, and thus not implantable," he explains. "Not having vasculature may be okay if you keep your tissue very small, but if you want bigger, thicker heart muscle, for example to use to repair an organ (implant), then you really need vasculature to deliver oxygen and nutrients to the tissue."

U of T spin-off to commercialize innovative person-on-a-chip technology

Boyang Zhang, University of Toronto
Boyang Zhang, University of Toronto
Photo courtesy of University of Toronto

"We are confident that no one else can grow mature heart tissue like we can, and growing mature tissue is important. Not just for implantation but also for drug trials. The closer the tissue is to adult tissue, the more accurate the test results," states Zhang. A spin-off company co-founded by Zhang, Radisic and counterparts from Columbia University called TARA Biosystems, is commercializing their technology, which they call "Bio-wire."

"There are pros and cons for different platforms, and there are also a lot of different tissues to focus on. When it comes to cardiac cells, I believe we are well ahead of our competitors," Zhang insists. And as an emerging medical technology that is believed to hold great promise, there is no lack of competition, with research teams around the globe, including from Boston, San Francisco, New York and the Netherlands all racing to develop and commercialize their own technology.

"Currently, we are working on scaling up the production process, which we expect to achieve within the next year to two years max. In the future, we are also looking at using this technology to grow kidney tissue, as the blood vessel barrier is very important." Soon, Zhang and Radisic's company will be in a position to establish an industrial process for setting up drug screening for pharmaceutical companies.

"To me, in the short term, organs-on-a-chip are a lot more realistic [than implantable tissue] because you can grow a tissue, which is similar in maturity to adult tissue, apply drugs and get an understanding of its toxicity and efficacy. It won't replace human and animal testing, but it will provide a valuable complement, because it enables one to see what might be going wrong in real time. When you observe an animal or human taking a drug, you may see a systematic effect, but it's hard to decouple the mechanism."

AngioChip will continue to be developed in Ontario

"The research started here, where we receive a great deal of support from the university and from the province of Ontario," says Zhang. But more importantly, explains Radisic, Ontario has remained at the forefront of regenerative medicine since U of T professors first demonstrated the existence of stem cells more than 50 years ago. "One cannot rely on getting human heart cells from patients through biopsy because they can't be proliferated and expanded in sufficient numbers, so you need to start with stem cells," says Radisic. "We rely on protocol and collaboration from Dr. Gordon Keller, Director of the McEwen Centre for Regenerative Medicine. He is one of the first people in the world to figure out how to do direct differentiation of pluripotent stem cells to cardiac tissue."

Learn more about the life-changing medical technology advances taking place in Ontario

September 9, 2016

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