Immune cells pave the way for advanced Heart-on-a-Chip Technology

Drs. Shira Landau, Yimu Zhao, and Milica Radisic are three of the primary authors of this research.

Researchers at the University of Toronto have made strides in heart disease research by incorporating primitive macrophages—a crucial immune cell—into heart-on-a-chip technology. This innovative approach promises to enhance the functionality and stability of engineered heart tissues, potentially transforming drug testing and disease modeling.

This research has been published in the latest issue of Cell Stem Cell.

One major challenge in creating bioengineered heart tissue is achieving a stable and functional network of blood vessels. Traditional methods have struggled to maintain these vascular networks over extended periods, limiting their effectiveness for long-term studies and applications.

Over the past decade, Professor Milica Radisic and her team have developed a miniaturized version of cardiac tissue on a platform called ‘heart-on-a-chip,’ which allows researchers to manipulate and test various drug formulations on heart tissue on a much smaller scale, saving resources and time.

In this new study, researchers integrated primitive macrophages derived from human stem cells into the heart-on-a-chip platforms. These macrophages, which resemble those found in the early stages of heart development, have shown remarkable abilities in promoting vascularization and enhancing tissue stability.

“We demonstrated here that stable vascularization of a heart tissue in vitro requires contributions from immune cells, specifically macrophages. We followed a biomimetic approach, reestablishing the key constituents of a cardiac niche,” added Professor Milica Radisic, one of the corresponding authors of the paper. “By combining cardiomyocytes, stromal cells, endothelial cells and macrophages we enabled appropriate cell-to-cell crosstalk such as in the native heart muscle.”

“The inclusion of primitive macrophages significantly improved the function of cardiac tissues, making them more stable and effective for longer periods,” said Shira Landau, a PhD candidate at the University of Toronto and one of the lead author of the study. The researchers also demonstrated that these macrophages could create stable, perfusable microvascular networks within the cardiac tissue, a feat that had previously been difficult to achieve.

Furthermore, the macrophages helped reduce tissue damage by mitigating cytotoxic effects, thereby improving the overall health and functionality of the engineered tissues.

This breakthrough has far-reaching implications for the field of cardiac research. By enabling the creation of more stable and functional heart tissues, researchers can better study heart diseases and test new drugs in a controlled environment. This technology could lead to more accurate disease models and more effective treatments for heart conditions.

The study was conducted by a multidisciplinary team of scientists at the University of Toronto, including experts in stem cell research, bioengineering, and cardiology. Their collaborative efforts have pushed the boundaries of what is possible in tissue engineering and regenerative medicine.