Bioengineered Heart Muscle Developed to Aid Cardiac Research

Originally Published MDDI September 2002

R&D DIGEST

Interdisciplinary research being conducted at the University of North Carolina at Chapel Hill (UNC) has reportedly resulted in the development of a bioengineered, rhythmically beating experimental model of heart muscle. According to the researchers, the model system is a bioartificial trabeculum (BAT), which functions similarly to the thin sections of tissue within the heart's main pumping chambers. Although still some distance away from any human clinical application, the model could prove a valuable scientific tool for exploring cardiac disease, including electrical and mechanical disturbances of the heart.

Says Wayne E. Cascio, MD, associate professor of medicine at UNC, "The purpose of our study was to explore the possibility that one could take isolated heart cells and under proper conditions allow them to coalesce and attach to each other in a functional way, thereby creating an artificial tissue." He adds that the researchers began to explore the potential of the BAT concept in response to a biomedical engineering lecture in which Albert J. Banes, MD, UNC professor of orthopedics, described his work on the development of artificial tendons. Banes had previously founded a company, Flexcell International (Hillsborough, NC), where he developed a special tissue plate that provides a framework in which cells in a liquid collagen gel can remodel on their own to form a more tissuelike structure.

Banes explains, "The fundamental basis for that company was a flexible bottom culture plate with the thought that all cells in tissues in our body are subjected to some forms of mechanical load, cyclic tension being one of them. We thought it would be better to grow cells in a dynamic environment, on a flexible substrate." He adds, "We could then stretch the tissue cells in a certain way to simulate the effects of mechanical loads on tendon, muscle bone, ligament, and cartilage, and also add the shear stress that occurs during fluid flow in blood vessels." Cascio thought cardiac myocytes could be grown and tissuelike cardiac muscle could be generated to test in culture in a similar way. "And that's where the collaboration began," Banes says.

The tissue model was developed by isolating cardiac myocytes from one-day-old rats. The myocytes then were mixed in a solution of collagen and serum, and allowed to gel under incubation in a Flexcell Tissue Train Plate. After being cultured for four days, the heart cells migrated toward the center of the gel to form a dense cord of tissue that extended between the two tethers.

According to the researchers, the tissue strand contracts at 100 beats per minute, which can be observed with a low-power microscope. The researchers conducted tests that indicated the presence of striations similar to those found in cardiac tissue. They also identified cell-to-cell coupling that is also characteristic of cardiac tissue.

The group hopes to apply the system to study the effects of mechanical loading on normal cardiac physiology and to develop a model system for the study of such cardiac illnesses as congestive heart failure.

Says Cascio, "In my lab, we're specifically interested in generating cardiac myocytes with certain electrical or contractile properties by manipulating the genetics of the cells, and then re-forming them into functional tissue to assess their properties."

Cascio also believes the model might be viewed by some as a method for generating tissue patches that can be applied to the surface of the heart, or for use in cardiomyoplasty procedures. "But this would be a very early stage of such an approach," he adds.

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