Israeli and Canadian scientists develop biological pacemaker

The natural pacemaker consists of designated pacemaker cells responsible for the contraction of the heart muscle.

By JUDY SIEGEL-ITZKOVICH
Updated: DECEMBER 16, 2016 00:34
The Technion (photo credit: Courtesy)
The Technion
(photo credit: Courtesy)
A biological cardiac pacemaker, whose efficacy has been demonstrated in rats and cell cultures, has been developed by researchers at the Technion- Israel Institute of Technology and Rambam Medical Center in Haifa together with a group of scientists in Canada.
Their study has just been published in Nature Biotechnology.
Prof. Lior Gepstein , a member of Technion’s Rappaport Faculty of Medicine, the chief of cardiology at Rambam and co-director of the research, said the biological pacemaker has many advantages over conventional electronic ones that are inserted via surgery, especially in their use to repair heart defects. Gepstein, a world leader in stem-cell research, presented a new approach to the treatment of irregular heartbeats.
The natural pacemaker consists of designated pacemaker cells responsible for the contraction of the heart muscle. Arrhythmia – irregular beats – can disrupt the functioning of the heart and lead to weakness, dizziness, fainting, heart failure and even death in some cases.
Over the years, electrical pacemakers have been developed to maintain a steady beat by correcting the diseased heart’s rhythm with electrodes connected to different parts of the heart.
However, this is carried out through invasive surgical procedures and involves a number of limitations, including insensitivity to hormones and the need to replace the battery from time to time. In addition, when children – whose hearts still growing – are the patients, the electrical pacemaker cannot suit itself to change as the volume of the heart increases.
One of the most promising alternatives to the electrical pacemaker is a biological pacemaker, based on the use of cells functionally similar to the natural pacemaker cells. However, due to technological limitations, an effective method for creating an efficient and reliable biological pacemaker had yet to be developed, until now.
The team used the information learned from developmental biology to develop a differentiation protocol for creating pacemaker cells from human embryonic stem cells. These can potentially turn into hundreds of mature cell types, such as muscle cells and bone cells. The researchers were able to direct the embryonic stem cells into becoming pacemaker-type heart cells. In lab experiments, Gepstein’s team demonstrated the efficacy of these cells as an alternative to natural pacemaker cells.
“The pacemaker cells generated from embryonic stem cells exhibit the same molecular, electrical and functional properties characteristic of human pacemaker cells. Thus we have an effective alternative to them when they go wrong,” Gepstein said. “The development is significant both in terms of research, because it involves investigating the heart in new ways, and the practical aspect – because we can create an ‘assembly line’ with an unlimited reservoir of pacemaker cells to treat patients with arrhythmia.”
After they completed successful tissue experiments, lab rats were used to show the effectiveness of the approach in living animals. The implant of pacemaker cells restored the heart rhythm to normal in six out of the seven rats tested.
“In the past, we used these cells, but until now they could not be manufactured cleanly. That is, there was a mixture of pacemaker cells and other heart cells. Here we present – together with Canadian partners – a method for manufacturing a pure population of pacemaker cells. This proves that they will function well as a substitute for damaged natural pacemaker cells,” Gepstein continued.
Gepstein and Dr. Udi Nosinobitz, his Technion and Rambam colleague, noted that the Canadian effort was led by Prof. Gordon Keller from the McEwen Center for Regenerative Medicine at the University of Toronto. Other partners were scientists from the University of Toronto and York University in Toronto.
The research was conducted within the cooperation agreement between the Technion and the University Health Network based in Toronto. Three years ago, the two established an international center for innovation in the study of cardiovascular systems, aimed at developing new ways to treat heart disease.