Linked to nearly all forms of heart disease is cardiac fibrosis, which typically follows damage to the heart and causes tissue to scar and stiffen, disrupting its ability to pump.

Yimu Zhao received an Education Fund grant in 2016 for her work in developing a platform to model cardiac fibrosis. She is leveraging the breakthrough work of Milica Radisic, who heads the University of Toronto’s Laboratory for Functional Tissue Engineering – and who has commercialized an “organ-on-a-chip” technology.

Meet the Biowire

The Radisic lab has created Biowire™, an innovative method of growing heart cells around a silk suture. Zhao’s work, funded by the Ted Rogers Centre for Heart Research, is a specific application of the Biowire™ platform – whose original plan was to use stem cells to generate 3-D heart tissues and screen their performance in response to drugs. They construct the tissues in such a way that they beat like the real human heart and allow functional assessments.

“The platform can be adjusted to whatever we aim to study,” Zhao said. “It can be used for many different conditions – and right now we think it is perfect to be used in fibrosis.”

To address this problematic condition, Zhao is constructing tissue in the 3-D model to mimic fibrosis in the heart, becoming stiff or even soft, depending on what cells and matrices are used. For this, she is using cardiomyocytes derived from human induced pluripotent stem cells and cardiac fibroblasts. She can then use various assessments to witness how cells react to that microenvironment.

This then becomes an important model to test-drive new therapies.

“Drugs are often withdrawn from the market due to serious toxicities and adverse cardiovascular effects,” Zhao said. “This platform resembles actual conditions in the heart and is a surrogate to safely test the therapeutic value of a drug or its toxicity.”

And that of course means new drugs come to market faster, investments are made in the right places, and the lives of patients are improved.

Zhao’s supervisor is Milica Radisic and collaborators on this project include Ted Rogers Centre Scientific Lead Craig Simmons (U of T) and Scientific Advisory Panel member Shoumo Bhattacharya (Oxford).