Researchers Demonstrate a Larger Heart Muscle Patch, but Generating Blood Vessels Remains a Challenge

In the engineering of tissue grown from a cell sample, researchers are currently limited to building thin slices or small sections, no more than a few millimeters in thickness, the distance that nutrients can perfuse without a capillary network. There is still no reliable, cost-effective solution for generating tissues that incorporate this intricate blood vessel network, and this is a roadblock to the creation of thicker, larger tissue sections. Thus the most advanced uses of tissue engineering at the present time are those in which thin tissue sections can still get the job done. One potential application is the generation of patient-matched cardiac tissue patches to augment the performance of a heart that has been damaged. These have been demonstrated to integrate with the living heart, replacing dead and scarred tissues that are no longer functional. This area of research is progressing quite well, as illustrated by this latest news.

Biomedical engineers have created a fully functioning artificial human heart muscle large enough to patch over damage typically seen in patients who have suffered a heart attack. The advance takes a major step toward the end goal of repairing dead heart muscle in human patients. "Right now, virtually all existing therapies are aimed at reducing the symptoms from the damage that's already been done to the heart, but no approaches have been able to replace the muscle that's lost, because once it's dead, it does not grow back on its own. This is a way that we could replace lost muscle with tissue made outside the body."

Unlike some human organs, the heart cannot regenerate itself after a heart attack. The dead muscle is often replaced by scar tissue that can no longer transmit electrical signals or contract, both of which are necessary for smooth and forceful heartbeats. The end result is a disease commonly referred to as heart failure. New therapies are needed to prevent heart failure and its lethal complications. Current clinical trials are testing the tactic of injecting stem cells derived from bone marrow, blood, or the heart itself directly into the affected site in an attempt to replenish some of the damaged muscle. While there do seem to be some positive effects from these treatments, their mechanisms are not fully understood. Fewer than one percent of the injected cells survive and remain in the heart, and even fewer become cardiac muscle cells.

Heart patches, on the other hand, could conceivably be implanted over the dead muscle and remain active for a long time, providing more strength for contractions and a smooth path for the heart's electrical signals to travel through. These patches also secrete enzymes and growth factors that could help recovery of damaged tissue that hasn't yet died. For this approach to work, however, a heart patch must be large enough to cover the affected tissue. It must also be just as strong and electrically active as the native heart tissue, or else the discrepancy could cause deadly arrhythmias. This is the first human heart patch to meet both criteria.

Finding the right combination of cells, support structures, growth factors, nutrients and culture conditions to grow large, fully functional patches of human heart tissue has taken the team years of work. Every container and procedure had to be sized up and engineered from scratch. And the key that brought it all together was a little bit of rocking and swaying. "It turns out that rocking the samples to bathe and splash them to improve nutrient delivery is extremely important. We obtained three-to-five times better results with the rocking cultures compared to our static samples." Tests show that the heart muscle in the patch is fully functional, with electrical, mechanical and structural properties that resemble those of a normal, healthy adult heart.

Researchers have already shown that these cardiac patches survive, become vascularized and maintain their function when implanted onto mouse and rat hearts. For a heart patch to ever actually replace the work of dead cardiac muscle in human patients, however, it would need to be much thicker than the tissue grown in this study. And for patches to be grown that thick, they need to be vascularized so that cells on the interior can receive enough oxygen and nutrients. Even then, researchers would have to figure out how to fully integrate the heart patch with the existing muscle. "We are actively working on that, as are others, but for now, we are thrilled to have the 'size matters' part figured out."


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