According to a new study from Cedars-Smidt Sinai’s Heart Institute, vesicles secreted by human heart cells may repair damaged tissue and prevent lethal heart rhythm disorders. The study, published in the European Heart Journal, could pave the way for a new approach to treating ventricular arrhythmia, a leading cause of sudden cardiac death. Experts describe the research as “poised to turn this entire field on its head” in an accompanying editorial. Ventricular arrhythmias can develop after a heart attack damages tissue, resulting in chaotic electrical patterns in the lower chambers of the heart. The heart eventually becomes so fast that it cannot support the circulation, resulting in a lack of blood flow and, if left untreated, death. The current options for treating ventricular arrhythmias caused by heart attacks are far from ideal. These include medications with severe side effects, implanted devices that deliver an electric shock, and radiofrequency ablation, a procedure in which parts of the heart are purposefully destroyed to disrupt disruptive electrical signals. Unfortunately, all of these have high recurrence rates. “An ablation is a counterintuitive approach because you are destroying heart muscle in an already weakened heart,” said Eugenio Cingolani, MD, senior author of the study and director of the Cardiogenetics-Familial Arrhythmia Program at Cedars-Sinai. “We thought, ‘What if, instead of destroying damaged tissue, we tried to repair it?’” With this in mind, the team set out to test a new approach in laboratory pigs that had suffered a heart attack. They injected some of the laboratory pigs with exosomes, which are tiny, balloon-like vesicles produced by cardiosphere-derived cells (CDCs), which are progenitor cells derived from human heart tissue. Exosomes are tough particles that contain molecules as well as the molecular instructions to make various proteins, making them easier to handle and transfer than parent cells or CDCs. Eduardo Marban, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and the Mark S. Siegel Family Foundation Distinguished Professor, was the first to develop and characterise CDCs. They’ve been used in a number of clinical trials for a wide range of diseases, most recently Duchenne muscular dystrophy. In one group of pigs, CDC-derived exosomes were injected into their hearts, while the other received a placebo. “The exosomes reduced the amount of scar tissue formed in the injured regions of the heart, normalising the rhythm without weakening the heart,” said co-author Dr. Marban. MRIs and tests to assess the electrical stability of the heart were performed on the animals. The laboratory pigs that had received the exosome therapy showed significantly improved heart rhythms and less scarring in their hearts four to six weeks after injection. Marine Cacheux, PhD, and Fadi G. Akar, PhD, both of Yale University, summarise the pros and cons of various experimental gene and cell-based approaches being studied for cardiac arrhythmias in an editorial published in the same issue of the European Heart Journal. According to Cacheux and Akar, Cedars-Sinai researchers “appear to have successfully combined the best features of cell and gene therapies to address a major unmet clinical need.” The authors note that Cedars-approach Sinai’s to repairing scarring in the heart is novel, and they describe the study as “a paradigm-shifting body of work.” Source: With inputs from ANI
