Towards an Exosome Therapy for Ventricular Arrhythmia­ in a Damaged Heart

The heart is of interest to a great many groups working on implementations of regenerative medicine, particularly in the context of alleviating the consequences of a heart attack. The scarring and damage of a heart attack can lead to ultimately fatal forms of arrhythmia, among other issues. Here, researchers discuss an exosome therapy approach to regenerating the damaged heart in order to address arrhythmia. Considerable progress has been made in recent years to adapt cell therapy approaches to the easier, more manageable use of exosomes derived from those cells. The exosomes carry signals that alter native cell behavior in much the same way as do transplanted cells. In most cell therapies the majority of the effect is due to signaling, not due to any work carried out by the cells introduced into the patient.

Ventricular arrhythmia­s can occur after a heart attack damages tissue, causing chaotic electrical patterns in the heart's lower chambers. The heart ends up beating so rapidly that it cannot support the circulation, leading to a lack of blood flow and, if untreated, death. Current treatment options for ventricular arrhythmia­s caused by heart attacks are far from ideal. These include medications with major side effects, implanted devices to provide an internal shock, and a procedure called radiofrequency ablation in which parts of the heart are purposely destroyed to interrupt disruptive electrical signals. Recurrence rates are, unfortunately, high for all of these.

Researchers sought to try a different approach in laboratory pigs that experienced a heart attack. They injected some of the laboratory pigs with tiny, balloon-like vesicles, called exosomes, produced by cardiosphere-derived cells (CDCs), which are progenitor cells derived from human heart tissue. Exosomes are hardy particles containing molecules and the molecular instructions to make various proteins, thus they are easier to handle and transfer than the parent cells, or CDCs. The animals were evaluated by MRI and tests to assess electrical stability of the heart. Four to six weeks after injection, the laboratory pigs that had received the exosome therapy showed markedly improved heart rhythms and less scarring in their hearts.


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