Cowen and team took skeletal muscle cells from rats and transferred them to a specially designed collagen scaffold. When in the scaffold, the cells align themselves into a conduit and express a protein that creates small pores between the cells, allowing them to transmit electrical signals.
When sections of this engineered tissue were transplanted into rat hearts, the new cells integrated into the existing heart tissue, making electrical connections with existing cells. (The rats did not have heart block; Cowen says rat hearts are too small to have pacemakers, which are necessary to keep a rat with heart block alive long enough to transplant the cells.) The researchers used optical imaging of the heart to show that the new cells were electrically active, essentially forming an alternative conduction circuit. The results appear in the July issue of the American Journal of Pathology.
Cowan and team are still working out some kinks in the therapy. They need to design a cell implant that will mimic the brief time delay of the AV node, which is crucial for proper heart functioning. They are now testing out different types of cells, such as stem cells from blood or bone marrow, which could be directed to differentiate into a cell that more closely resembles a heart cell. The scientists initially chose skeletal muscle cells because they’re an easily acquired resource – such cells could be obtained from patients needing a pacemaker by a routine muscle biopsy and don’t need to be cultured under special conditions, as is the case with stem cells.
The researchers are also testing the therapy in larger animals, whose hearts more closely resemble those of humans. They will induce heart block in these animals and implant them with both pacemakers and engineered skeletal tissue to determine if the engineered tissue can take over for the pacemaker.
“The less hardware you put in someone, the better,” says Ivan Vesely, a biomedical engineer who specializes in cardiac tissue engineering at Children’s Hospital Los Angeles. “So if the only problem is a missing conduction pathway, it makes a lot of sense to try to reengineer that pathway, rather than turning the whole heart over to a pacemaker.”