The Potential of Human iPSC-Heart Cells in Fentanyl Opioid Research

Fentanyl, a potent synthetic opioid that is 50 to 100 times stronger than morphine, has become a significant contributor to the ongoing opioid crisis. Its overdose effects include severe respiratory depression and, notably, cardiac arrest. While opioid-related arrhythmias are known, the specific impacts of fentanyl on heart rhythm have yet to be thoroughly examined.

Recent research published in Circulation by researchers from Stanford Cardiovascular Institute highlights the groundbreaking use of human-induced pluripotent stem cell (iPSC) derived heart cells to study fentanyl’s cardiac effects. Led by first-author Gema Mondéjar-Parreño, Ph.D., and senior author Joseph C. Wu, MD, Ph.D., the study leverages patient-specific iPSC-cardiomyocytes to analyze electrophysiological changes induced by fentanyl.

The researchers analyzed 19 toxicology studies conducted between 1994 and 2022, which indicated fentanyl concentrations in overdose scenarios were approximately three times higher than therapeutic doses used in chronic pain management. In the lab, iPSC-derived cardiomyocytes were exposed to fentanyl doses simulating overdose conditions. The results revealed significant disruptions in calcium signaling—a vital process for heart muscle contractions—and a slowing of the cells' readiness for the next beat, leading to irregular heart rhythms.

Moreover, the study demonstrated that when combined with isoproterenol, a drug that increases heart rate, fentanyl-induced arrhythmias worsened, suggesting that heightened sympathetic stimulation can aggravate fentanyl's cardiac effects.

This research provides critical evidence that fentanyl impairs cardiac cell function, leading to rhythm disturbances that can precipitate sudden cardiac events. These electrophysiological alterations, coupled with respiratory depression, underscore fentanyl’s high risk for causing cardiac arrest especially in overdose cases.

Further investigations are essential to deepen our understanding of fentanyl’s impact on cardiac electrophysiology and to develop targeted strategies for preventing fentanyl-related cardiac emergencies. The innovative use of human iPSC-cardiomyocytes offers a promising avenue for personalized medicine and safer therapeutic interventions in the future.

Source: https://medicalxpress.com/news/2025-08-exploring-human-ipsc-heart-cells.html