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Tissue-Patching a Broken Heart

Multi-university consortium nabs $8.6 million to build the world’s first three-dimensional, fully functional heart patch

Nenad BursacA multi-university team of researchers has been tasked with creating and testing a three-dimensional “heart patch” that can literally mend a broken heart.

Unlike many human tissues, the heart cannot regenerate functional muscle tissue after a heart attack or disease has killed part of the muscle wall. The dead tissue can no longer transmit electrical signals necessary for smooth heartbeats and can strain the surrounding muscle, leading to 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 heart in an attempt to replenish some of the damaged tissue. While there does seem to be some positive effects from this treatment, their origins are unknown as these stem cells do not survive for long and cannot become functional cardiac muscle cells.

Tissue engineers believe there is a better way. By strategically placing pluripotent stem cells that can be grown into any cell type into engineered scaffolding, a three-dimensional “heart patch” can be grown that features complex tissue closely resembling native heart muscle.

These patches could then be implanted and theoretically perform all of the functions of a healthy, beating heart muscle. The approach is expected to improve cell survival upon implantation, retain more of the cells at the damaged site and release molecules that can help the heart repair more efficiently than current clinical trials that simply inject free stem cells.

But there are many obstacles standing between current research and successful implementation.

The National Institutes of Health has turned to Duke University, the University of Alabama at Birmingham and the University of Wisconsin—Madison to overcome these hurdles. The consortium was recently awarded a seven-year, $8.6 million grant to develop and test such heart patches in live animals.

“We are very excited about this opportunity to move our longstanding research in cardiac tissue engineering toward clinical practice to help patients,” said Nenad Bursac, professor of biomedical engineering at Duke. “Translating this approach to clinics will require overcoming several important challenges, and will demand every bit of combined expertise that Duke, UAB and UW-Madison have to offer.”

The difference between previous attempts to heal human heart tissue and the new project is the advent of embryonic and induced pluripotent stem cells. These technologies provide the ability to engineer all of the specific cell types that make up heart muscle: cardiomyocytes, the cells responsible for muscle contraction; fibroblasts, the cells that provide structural framework to tissue; and endothelial and smooth muscle cells, the cells that form blood vessels.

Bursac and colleagues at Duke will lead the effort to take these human cells and embed them into patches large enough to help real-life patients. This will require making sure the different cell types are present in the correct ratios and that the patch is able to quickly assemble, become functional and fully integrate with the existing tissue’s blood supply and electrical signals.

Besides forming functional muscle akin to natural heart tissue, this approach will allow researchers to personally tailor the therapy to individual patients.

Joining Bursac in his efforts from the Duke University School of Medicine are Howard Rockman, the Edward S. Orgain Professor of Cardiology, and Victor Dzau, the James B. Duke Professor of Medicine.

“The ability to make functional heart muscle tissue from pluripotent stem cells is crucial to directly helping a diseased heart’s functionality,” said Bursac. “This is a feat that cannot be achieved using current cell sources in clinical trials because they cannot become functional cardiac muscle cells. The field is expected to benefit from use of engineered heart tissues, which is where Duke and our lab come in as leaders in the field.”

Directing the consortium is Jianyi “Jay” Zhang, chair of the UAB Biomedical Engineering Department, who will also lead a team to test the heart patches in a pig model of cardiovascular disease, a close approximation in an animal to the human heart.

UW-Madison’s effort is led by Timothy J. Kamp, a UW-Madison cardiologist and co-director of the UW–Madison Stem Cell and Regenerative Medicine Center. Their role in this endeavor is to use stem cells to create the main cell types that compose heart tissue while ensuring these cells do not prompt an immune response.