First biological pacemaker developed

Scientists have developed the first functional pacemaker cells from human stem cells which can regulate heart beats with electrical impulses, paving the way for alternate, biological pacemaker therapy.

The findings from the McEwen Centre for Regenerative Medicine at University Health Network in Canada show how human pluripotent stem cells can be coaxed in 21 days to develop into pacemaker cells. These human pacemaker cells were tested in rat hearts and were shown to function as a biological pacemaker, by activating the electrical impulses that trigger the contraction of the heart.

Pluripotent stem cells have the potential to differentiate into more than 200 different cell types that make up every tissue and organ in the body. Sinoatrial node pacemaker cells are the heart's primary pacemaker, controlling the heartbeat throughout life.Defects in the pacemaker can lead to heart rhythm disorders that are commonly treated by implantation of electronic pacemaker devices.

Learning how to generate pacemaker cells could help in understanding disorders in pacemaker cells, and provide a cell source for developing a biological pacemaker. Biological pacemakers represent a promising alternative to electronic pacemakers, overcoming such drawbacks as a lack of hormonal responsiveness and the inability to adapt to changes in heart size in pediatric patients.

The researchers used a developmental-biology approach to establish a specific protocol for generating the pacemaker cells. "What we are doing is human biology in a petri dish. We are replicating nature's way of making the pacemaker cell," said Dr Gordon Keller, Director of the McEwen Centre. Based on previous findings in animal models, the researchers tested and mapped out the specific developmental pathway of how human pluripotent stem cells become pacemaker cells.

This was achieved by testing different signalling molecules at different times throughout the 21 days to guide the cells towards their goal. "It's tricky. You have to determine the right signalling molecules, at the right concentration, at the right time to stimulate the stem cells," said Stephanie Protze, a post-doctoral fellow in the laboratory of Keller. The study was published in the journal Nature Biotechnology.