Researchers reprogram fat-derived stem cells to act as biologic pacemakers

Researchers at the University of Houston are pioneering a unique method for developing biological pacemakers: converting stem cells found in fat to biologic pacemaker cells.

Pharmacologist and UH associate professor Bradley McConnell, BS, PhD, is leading the effort and published his team’s latest results in the Journal of Molecular and Cellular Cardiology. The results build on colleague and co-author Robert J. Schwartz’s 2012 finding that adipogenic mesenchymal stem cells in fat tissue could be reprogrammed into cardiac progenitor cells.

Those same progenitor cells are now being programmed by McConnell et al. to act as biologic pacemaker cells—cells responsible for keeping hearts beating as a sinoatrial node (SAN), part of the electrical cardiac conduction system (CCS). According to a release from UH, the SAN is the heart’s primary pacemaker and houses a person’s native cardiac pacemaker cells; if blockage or failure occurs at any point, it can result in dangerous arrhythmias.

To convert stem cells in vitro, McConnell and colleagues infused the cells with a combo of three transcription factors—SHOX2, HCN2 and TBX5 (SHT5)—and a plasma membrane channel protein. 

“We are reprogramming the cardiac progenitor cell and guiding it to become a conducting cell of the heart to conduct electrical current,” McConnell said in the release. “The combination will facilitate the development of cell-based therapies for various cardiac conduction diseases.”

He said biological pacemakers are a favorable alternative to the 600,000 electronic pacemakers that are implanted in patients annually, because they don’t need to be regularly checked by a physician and won’t wear over time.

“Batteries will die. Just look at your smartphone,” McConnell said. “This biologic pacemaker is better able to adapt to the body and would not have to be maintained by a physician. It is not a foreign object. It would be able to grow with the body and become much more responsive to what the body is doing.”