Pacemaker from Stem Cells Receives Research Funding

(SACRAMENTO, Calif.) - Deborah K. Lieu, a stem cell scientist in cardiovascular medicine at UC Davis Health System, has received a $1.3 million research grant from the California Institute for Regenerative Medicine (CIRM) to develop stem cells that could serve as a biological alternative to the electronic pacemakers that people now use to regulate heart rhythm.

According to Lieu, each year 350,000 cardiology patients with abnormal heart rhythms receive electronic pacemakers to maintain a normal heart beat. The devices, while effective, have several disadvantages, including limited battery life and poor response to changing heart rates, such as when a person is exercising. Lieu, who is working with colleague Nipavan Chiamvimonvat, the Roger Tatarian Endowed Professor of Cardiovascular Medicine at UC Davis, plans to examine ways to improve the generation of pacemaking cells using human-induced pluripotent stem cells (hiPSCs), potentially creating what she calls a "biopacemaker."

"There are more than 3 million patients around the country who are dependent on electronic pacemakers," said Lieu. "Each one costs about $58,000 to implant and requires follow-up surgery about every 5 to 10 years to change batteries. Creating a biopacemaker from stem cells would avoid the burden of battery replacement and provide the physiological benefit of enabling a person's heart to naturally adapt to a rising heart rate during activities such as exercise."

Lieu's grant was among more than two dozen projects that received support from state stem cell agency's governing board last week as part of CIRM's Basic Biology awards program. The funding focuses on basic research projects that can provide a better understanding about the fundamental mechanisms of stem cell biology and move researchers closer to knowing how best to use stem cells to help patients.

To create the pacemaking cells, Lieu and her colleagues plan to manipulate an ion channel (the SK channels in cardiac myocytes) to alter the calcium signaling mechanisms during hiPSC differentiation. Stem cell scientists create hiPSCs - typically from an adult cell such as a skin cell - by inducing a "forced" expression of specific genes. Once reprogrammed, the cells take on a variety of capabilities (becoming pluripotent) and offer a range of stem cell treatment possibilities.

Development of a biopacemaker could also benefit the one-in-20,000 infants and premature babies suffering from congenital heart-rhythm dysfunction who currently are not suitable candidates for electronic pacemakers. Infants are physically too small for the device. A biological pacemaker could fit with their small stature and then grow as the infant grows.

Collaborating with Lieu and Chiamvimonvat on the research project will be Jan Nolta, director of the UC Davis Institute for Regenerative Cures; Donald Bers, chair of the UC Davis Department of Pharmacology; and James Chan, assistant professor in the Department of Pathology and affiliated with the NSF Center for Biophotonics Science and Technology at UC Davis.

UC Davis is playing a leading role in regenerative medicine, with nearly 150 scientists working on a variety of stem cell-related research projects at campus locations in both Davis and Sacramento. The UC Davis Institute for Regenerative Cures, a facility supported by the California Institute for Regenerative Medicine (CIRM), opened in 2010 on the Sacramento campus. This $62 million facility is the university's hub for stem cell science. It includes Northern California's largest academic Good Manufacturing Practice laboratory, with state-of-the-art equipment and manufacturing rooms for cellular and gene therapies. UC Davis also has a Translational Human Embryonic Stem Cell Shared Research Facility in Davis and a collaborative partnership with the Institute for Pediatric Regenerative Medicine at Shriners Hospital for Children Northern California. All of the programs and facilities complement the university's Clinical and Translational Science Center, and focus on turning stem cells into cures. For more information, visit http://www.ucdmc.ucdavis.edu/stemcellresearch.

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Pacemaker from Stem Cells Receives Research Funding