At the American Heart Association Scientific Sessions meeting this week, Hee Cheol Cho’s lab is presenting three abstracts on pacemaker cells. These cells make up the sinoatrial node, which generates electrical impulses driving our heart beats. Knowing how to engineer them could enhance cardiologists’ ability to treat arrhythmias, especially in pediatric patients, but that goal is still some distance away.
Just a glimpse of the challenge comes from graduate student Sandra Grijalva’s late breaking oral abstract describing “Induced Pacemaker Spheroids as a Model to Reverse-Engineer the Native Sinoatrial Node”, which was presented yesterday.
Cho has previously published how induced pacemaker cells can be created by introducing the TBX18 gene into rat cardiac muscle cells. In the new research, when a spheroid of induced pacemaker cells was surrounded by a layer of cardiac muscle cells, the IPM cells were able to drive the previously quiescent nearby cells at around 145 beats per minute. [For reference, rats’ hearts beat in living animals at around 300 beats per minute.]
Conclusion: iPM-spheroids can pace and drive surrounding quiescent myocardium, overcoming the source-sink mismatch. The iPM-spheroids are viable in long-term and exhibit native SAN [sinoatrial node]-like pacemaker cell organization. These data provide an in vitro platform on which the design principles of native SAN could be tested.
A little more context can be found in Sandra’s F31 doctoral grant.
Another presentation yesterday was from postdoc Jin-mo Gu on the metabolic profile of induced pacemaker cells. A third today from pediatric cardiologist Nam Kyun Kim discusses a parallel approach to engineering pacemakers in culture: recreating them in the heart in situ with TBX18 gene transfer, combined with an additional measure to keep the induced pacemaker cells “disciplined.”
Lab Land looks forward to learning more about this innovative research. Cho is the Urowsky-Sahr Scholar in Pediatric Bioengineering and an associate professor in pediatrics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory.