Tissue-engineered cells transmit electrical signals in animal hearts

American Heart Association meeting report

Preliminary findings of a study in rats suggests that a person’s own cells might one day replace artificial pacemakers, researchers reported today at the American Heart Association’s Scientific Sessions 2002.

Studies conducted at Children’s Hospital Boston tested the ability of immature skeletal muscle cells to interconnect with heart cells and spread the electrical impulses that keep the heart beating properly.

“The cells have survived in rats for more than a year and they appear to have made connections with cardiac cells,” says Douglas B. Cowan, Ph.D., a cell biologist who led the study. “The electrical pathway developed within 10 weeks of implantation.

“Ultimately – maybe a decade down the road – we may be able to use such cell-based technologies in humans to free them from cardiac pacemaker devices,” says Cowan, also an assistant professor of anesthesia at Harvard University Medical School in Boston.

Heart contraction starts with an electrical signal that begins in the atrium, a tiny area of the heart’s upper-right chamber. The signal then moves to the other chambers. Damage to the electrical pathway between the atrium and ventricles (the lower chambers) can result in complete heart block, a potentially fatal condition that can only be treated by implanting a cardiac pacemaker.

“We have gathered preliminary evidence that immature skeletal muscle cells can establish a pathway to transmit electrical signals from the heart’s upper right chamber to its lower right chamber,” he says.

Heart block is present in about one in 22,000 births, Cowan says. It also can result from open-heart surgery in children, or develop later in life. It’s particularly difficult to treat in infants and children, he says.

“You can’t feed pacemaker wires through the blood vessels of some pediatric patients because the vessels are too small,” he explains.

The wire must be coiled inside the chest so it can expand as the child grows, and the pacemakers or their wires often fail, which results in further surgery.

“These patients usually face several repair or replacement operations over the course of their lives,” Cowan says.

Researchers extracted small amounts of skeletal muscle from the rats to obtain myoblasts, immature cells destined to become muscle. Unlike mature skeletal muscle cells, myoblasts can make the same proteins that heart muscle cells use to connect with one another to transmit electrical signals. The team used engineered tissue containing about 70 percent myoblasts and 30 percent other cell types, using the connective tissue called collagen. Tissue engineering involves removing cells from the body, manipulating them in the laboratory to create a specific tissue, such as a piece of bone for reconstructive surgery, and implanting it into the patient.

The team created three-dimensional strips of tissue by growing the cell mixtures in small tubes cut in half lengthwise. They then surgically implanted the strips in rat hearts.

“We used a general shape and cells from other animals, but the idea is that eventually we could custom grow tissue for a person using his or her own cells,” Cowan notes. By using the patients’ own cells, clinicians may avoid the risk that the immune system will attack the implanted cells, he says.

“The biggest theoretical weakness in this idea was that the proteins required to connect one heart cell to another – called connexins – are usually not expressed in mature skeletal muscle,” Cowan says. “Connexins are very important to conduction in the heart. They modify the speed and direction of the electrical signals, and greatly influence how they flow from cell to cell.”

“The other question was whether these cells would actually connect with cardiac cells to form an electrical pathway,” he says.

Today, the research team reported that the pathway developed and the connexins were present and functioning in the implanted tissue more than one year later.

“We are now using much more sophisticated measurements to confirm this phenomenon and everything at this point shows that the electrical pathway is there,” Cowan says.

A lot of work remains before researchers can test the cell-implant technique in humans, Cowan says. “We need rigorous, state-of-the-art experiments to confirm that the tissue is functioning and that the same thing can happen in larger animals.”

Co-authors are Yeong-Hoon Choi, M.D.; Christof Stamm, M.D.; Mara Jones, M.S.; Francis X. McGowan, Jr., M.D.; and Pedro J. del Nido, M.D.