Regenerating a broken heart

Author: Guest, 02/11/16

Samantha is a PhD student in the Chemical Engineering and Applied Chemistry department at the University of Toronto. She has previously investigated regeneration in a non-mammalian gecko model during an MSc program, and now currently combines stem cell biology and biomaterials to encapsulate and deliver therapeutic cells to the stroke-injured brain. Samantha became interested in scientific communication as a means to combine her love of writing and science to share exciting scientific discoveries to a broader community. Follow Samantha on Twitter @samantha_lpayne


heart-667806_640As the universal symbol of love and affection, representations of the heart are abundant this month as Valentine’s Day approaches. A simple graphical depiction doesn’t nearly represent the complexity of the heart as an organ – atria, ventricles and valves all working constantly to sustain life. The heart is composed of various cell types, the majority of which are cardiomyocytes, which must coordinate to pump blood throughout the body.

But what happens when something goes wrong? During an event such as a heart attack, tissue oxygen levels are depleted, causing death of cardiomyocytes and tissue damage. In lower order life forms like fish and newts, adult cardiomyocytes can de-differentiate into immature cells and proliferate to replace the lost tissue. Unfortunately for mammals, we lack this capacity for plasticity and proliferation. So how can we repair a damaged heart?

To replace lost cardiomyocytes and other cell types, regenerative medicine strategies have focused on delivering new cells directly to the heart. However, achieving successful delivery and functional regeneration is no easy task. Aside from the hurdle of creating functionally mature cardiomocytes, the cells need a substrate for delivery that will support survival and localize them to the area of injury, as delivery of cells alone results in widespread death. To accomplish this, bioengineers are developing new materials and delivery strategies.

When the heart tissue becomes damaged, an ischemic and inflammatory environment is created that is extremely hostile to cells. In addition, there is a lack of extracellular matrix (ECM) for cells to anchor to. Encapsulating cells in a biomaterial can both protect cells from the environment and provide anchorage.

One example of a class of biomaterials often used is hydrogels (hydrophilic polymer chains). Hydrogels can protect and support cells for delivery and have the added bonus of being injectable, meaning that they can be delivered in a clinically-relevant catheter system. Among the hydrogels studied for heart regeneration is alginate, which is composed of a polysaccharide found in algae, and has been shown to improve cardiac function in a rat myocardial infarction model using human mesenchymal stem cells.

Another strategy for cell delivery is the use of a more solid scaffold that cells can be seeded onto. The orientation and organization of how the cells are delivered is important for proper electrical conduction in the heart; scaffolding allows cells to be arranged properly before implantation, rather than relying on cells to migrate once in the heart.

An innovative scaffold system, known as Tissue-Velcro, has recently been developed by Milica Radisic’s group at the University of Toronto (read more about it here). This system takes its inspiration from everyday Velcro and is composed of honey comb patterned microscopic loops and hooks formed out of biodegradable materials. Cells are seeded on successive 2D layers of the scaffold and assembled into a 3D structure that can recreate the cellular orientation found in the heart.

Amazingly, the group was even able to demonstrate that the cardiomyocytes will beat in synchrony almost immediately upon layer assembly. Not only can this strategy allow us to transplant cells into the heart, but it can also facilitate studying cardiomyocyte function in vitro. With this strategy and others, exciting new options are opening up in the field of cardiac regeneration that could prove successful in the future. Be still my beating heart.

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