U of T PhD research maps optimal conditions for heart tissue development 

The human heart contains more than five billion cells. Yet, when someone experiences heart failure, the tissue has almost no ability to regenerate.   

For patients with end-stage heart failure, the gold-standard treatment is organ transplantation. But transplants come with two major obstacles: a lifelong reliance on immunosuppressant drugs to prevent rejection and a chronic shortage of donor organs. According to the Canadian Institute for Health Information, 190 people in Canada were on a waiting list for a heart transplant as of Dec. 31, 2024. 

Growing tissues in vitro or in vivo has long been an alternative researchers hope to refine, but the work is costly and complex. A single run of the experiment (which happens over the course of a couple days) could cost up to $5,000.  

To address these barriers, Ferdinand (Reke) Avikpe is using computational modelling to identify the biochemical and mechanical conditions that allow heart cell tissue to grow efficiently in the lab.   

“By identifying the best biochemical and mechanical conditions, researchers can design lab experiments that yield higher-quality cells while minimizing costs,” says Avikpe, a PhD candidate at the Institute of Biomedical Engineering (BME) at the University of Toronto.     

Avikpe is conducting this work in the ATOMS Laboratory, and is supervised by University Professor Cristina Amon, dean emerita of the Faculty of Applied Science and Engineering. The project is part of Project MaVen, a New Frontiers in Research Fund-supported, multi-institutional collaboration to advance stem cell-based heart repair, whereAmon is a co-principal investigator. 

Avikpe is working on models to map how pluripotent stem cells proliferate and change into heart cells, which will be used to predict what path they take and when the change happens. 

Considering biochemical factors, one key ingredient is glucose, which is a primary energy source for cell growth. As cells consume glucose, they produce lactate as a byproduct. Monitoring glucose and lactate levels is essential to maintain a healthy environment for cell growth as high levels of lactate in bioreactor medium can become toxic and harm cells. 

Avikpe is also monitoring aggregate size, which refers to spherical clusters of cells that play a key role in regulating the signaling environment required to become heart cells.Larger aggregates can limit access to nutrients and oxygen. While microscopic in size, there is a “just right” range – too large and the inner cells suffer, too small and key cell-cell signals are lost.  

“Literature has shown that beyond a certain size, internal cells in aggregates become necrotic because they don’t get enough nutrients,” Avikpe says. “We’re tracking aggregate size to determine the optimal size where cells can constantly receive all the nutrients they need to grow.” 

Cells are grown in a bioreactor, which, in terms of mechanical cues, are subject to an important factor called shear stress. This occurs when fluid movement or stirring produces forces parallel to the surfaces of cells or particles.  

Avikpe works with two bioreactor systems, with capacities of 100 millilitres and 500 millilitres. Each system can grow at least one million cells per millilitre. 

“Moderate levels of shear stress have been shown to help enhance the growth of the cells. However, when the levels of shear stress are high, they will disrupt the cell membranes,” Avikpe says.  

A similar trend happens with energy dissipation, which promotes cell mixing. Researchers describe low levels as gentle fluid motion that allows cells to settle, moderate levels as steady circulation that keeps cells evenly mixed, and high levels as vigorous motion that generates damaging shear forces. 

“In the same way, a high energy dissipation rate will lead to high shear, a low energy dissipation rate will mean that there is not enough cell mixing and no uniform distribution of nutrients,” Avikpe says. 

Avikpe is continuing to work on the model to next understand cell differentiation, which will help predict when stem cells transition into functional heart cells under different culture conditions. 

“By capturing all these biological and mechanical factors in the model, we can pinpoint the optimal and most cost-effective conditions for growing cells,” Avikpe says. “This means that researchers can design better and more affordable experiments, moving us closer to creating reliable cell-based therapies for repairing heart tissue.” 

BRN Brilliance is a multimedia series produced by the Black Research Network. The series spotlights Black-led interdisciplinary research, teaching and collaboration at the University of Toronto.