Recent research suggests that stem cell–derived cardiac cells may enhance the treatment of heart disease. Peter Zandstra, professor in the Institute of Biomaterials and Biomedical Engineering at U of T and Canada Research Chair in stem cell bioengineering, collaborated with professor Milica Radisic and Gordon Keller’s research group at the University Health Network to develop engineered heart tissue and cardiac myocytes (commonly known as cardiac cells). These cells effectively mimic certain features of heart tissue.
Zandstra and Radisic recreated the heart’s environment in the lab to better understand how individual cardiac myocytes integrate with each other. “[To do this] we created an artificial cardiac patch, into [which] we injected different test cell populations under different conditions. We found the progenitor cell integrates [most efficiently],” says Zandstra. The progenitor cell is derived from a stem cell. It is more developed than the stem cell it originated from, but not as mature as an adult cardiac myocyte.
The progenitor cell proliferates during the adolescent phase, allowing it to easily integrate in the engineered heart tissue. Its stem cell counterpart is too dissimilar from the adult cardiac myocyte found in the heart tissue, thus it does not possess the ability to integrate successfully. Similarly, mature cardiac myocytes are too undifferentiated to proliferate.
“[Although] these [adult] cells function very well in heart tissue, they die during a heart attack. When one transplants adult cells, they [lack] the developmental capacity to reconnect with the [other] adult cells,” explains Zandstra. This failure to reconnect occurs because adult cardiac cells are not accustomed to receiving signals from the heart tissue, and are therefore unable to locate where they are within the tissue itself.
Additionally, the progenitor cell must follow the rhythms of the tissue in which it integrates, or rather it must be electro-mechanically equivalent to the host tissue. “If a cell creates its own rhythms, it might create a cardiac arrhythmia which is problematic to the heart,” says Zandstra. Cardiac arrhythmia can lead to cardiac arrest and sudden death. Moreover, the cell must be capable of generating the same contraction forces as the host tissue. If the injected progenitor cell lacks the mechanical strength of contraction, it may weaken the heart as a whole.
Progenitor cells were injected into the engineered heart tissue fabricated from neonatal mouse or rat heart cells to test the integration. The engineered heart tissue acted as a scaffold onto which the injected cells attached. “Electrical [stimulation] of the scaffold caused the cells to realign and start to function as a [whole] piece of tissue,” explains Zandstra.
“[Prior to this research] no one had used engineered heart tissue to screen cell transplantation of progenitor cells,” says Zandstra. “Most people tried to inject tissue right into the heart, but hadn’t been able to understand how cells integrate with each other.” Injecting cells directly into an animal heart is difficult since the environment cannot be controlled. Recreating the environment in a dish allows researchers to observe and analyze the integration of cardiac cells.
While Zandstra acknowledges that the in vitro recreation of cell cultures in two dimensions was successful, he believes that the three-dimensional environment of the tissue they have created is more advantageous since it better mimics the heart’s environment.
The study was funded by the Heart and Stroke Foundation and published in Proceedings of the National Academy of Sciences in 2009. This research offers a way to screen various cell types that could be used for cardiac therapy. “We are hoping that the results we are generating in this model will accelerate the development of new therapies,” says Zandstra.
