The cells distributed themselves evenly in the tissue and oriented themselves in the same direction. Tested in the laboratory, the engineered tissue started beating when stimulated electrically, and its muscle cells produced proteins called connexins that channel ions from cell to cell, connecting the cells electrically.
When the engineered tissue was implanted into rats, between the right atrium and right ventricle, the implanted cells integrated with the surrounding heart tissue and electrically coupled to neighboring heart cells. Optical mapping of the heart showed that in nearly a third of the hearts, the engineered tissue had established an electrical conduction pathway, which disappeared when the implants were destroyed. The implants remained functional through the animals' lifespan (about 3 years).
"The advantage of using myoblasts is that they can be taken from skeletal muscle rather than the heart itself--which will be important for newborns whose hearts are so tiny they cannot spare any tissue for the biopsy--and that they're resistant to ischemia, meaning they can go without a good blood supply for a relatively long period of time," Cowan says.
Cowan and his team are now working with a large-animal model that more closely simulates pediatric heart block. Further studies will seek to create tissue-engineered grafts that behave more like a natural AV node, for example by providing a built-in delay before sending electrical signals to the ventricles. The team is investigating whether other cell types, such as stem cells derived from muscle or bone marrow, might be made to behave more like AV node cells.
Complete heart block is present in about 1 in 22,000 births. It can also result from congenital heart disease, through an injury or scar tissue from heart surgery, or as a side effect of medications. In adults, pacemakers are a good solution, but in children, they carry a grea
Contact: Jamie Newton
Children's Hospital Boston