Biological pacemakers created from human embryonic stem cells or transcription factor-driven reprogramming in a preclinical model of heart block

Funding Type: 
New Faculty Physician Scientist
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Electronic Pacemakers (EP) have been used for over 50 years for the treatment of cardiac conditions associated with slow heart rates,such as complete heart block. Despite continuous refinement,the presence of a foreign body increases the risk of hardware related infections. This serious complication is associated with an increased risk of generalized infection,and death. Treatment of these infections often requires complete removal of all hardware and treatment with intravenous antibiotics for over two weeks. In some patients,inserting a temporary pacing device to maintain an adequate heart rhythm until the infection is cleared and a permanent device re-implanted, is required. Biological pacemakers (BioPs) have been developed as an alternative to EP to treat these conditions. By using stem cell-based approaches, the patient's own pacemaker cells can be regenerated, avoiding the need for an EP. We have developed a clinically-applicable delivery technique to study different BioPs strategies experimentally.In the case of device-related infections,a BioP could provide the patient with adequate heart rates while the infected device is removed and infection is cleared. This could improve the therapeutic efficacy by removing any possible nidus of infection associated with a temporary pacing device. Development of a BioP for the focused "bridge to device" application could open the way for more ambitious applications such as definitive replacement of EP by biological surrogates.

Statement of Benefit to California: 

The numbers of cardiac pacemakers and defibrillators implantations for treating cardiac rhythm disorders continue to rise steadily in the United States.Despite continuous refinement, complications such as device malfunction and infection occur.Device-related infections have been rising in the past decade not only due to the increase in device implantations, but also due to a higher incidence of bacterial infections in the US and worldwide.Current treatment for these conditions involves admission to the hospital,removal of all infected hardware,placement of a temporary pacing device (in those pacer-dependent patients),and treatment with systemic antibiotics.This increases the risk of generalized infections, hospitalization length, patient’s discomfort, and health care costs.New and more effective treatment modalities for these conditions are needed. Clearly, all Californians stand to benefit, directly or indirectly, from the development of more effective treatment modalities for heart rhythm disorders. The present work seeks to provide the scientific basis for regulatory filings that would allow regenerating the patient’s own pacemaker cells avoiding the need for an electronic pacing device.This could potentially offer a more effective treatment option for Californians inflicted by pacemaker-related complications.By reducing hospitalization length, this may also reduce the economic burden presently borne by taxpayers who support the health care systems in California.