The first human heart cells that can be paced with light were created at Stanford University, providing new insight into the vital organ's function. To create the light-responsive heart cells, the researchers first inserted DNA encoding a light-sensitive protein known as channelrhodopsin-2 (ChR2) into human embryonic stem cells. ChR2 controls the flow of electrically charged ions into the cell. The primary ion for heart cells is sodium, which initiates the electrochemical cascade that causes the cell to contract. They then transformed the optogenetically engineered stem cells into cardiomyocytes that respond to light. Stanford researcher and co-author of the study, Dr. Oscar Abilez, is the first to create optogenetic human heart cells. The all-important protein for the experiment is ChR2, which is sensitive to a very specific wavelength of blue light and regulates tiny channels in the cell surface. When ChR2 is illuminated by the right wavelength of blue light, the channels open to allow an influx of electrically charged sodium into the cell, producing a contraction. Oscar Abilez and a multidisciplinary team at Stanford University developed the first human heart cells that can pulse in response to specific types of light. (Image: Norbert von der Groeben) The researchers then used algorithms to test their new cells in a computer simulation of the human heart, injecting the light-sensitive cells in various locations in the heart and shining a virtual blue light on them to observe how the injections affected contraction as it moved across the heart. “In a real heart, the pacemaking cells are on the top of the heart, and the contraction radiates down and around the heart,” said Ellen Kuhl, co-author of the study and a specialist in sophisticated computer modeling of the human body. “With these models, we can demonstrate not only that pacing cells with light will work, but also where to best inject cells to produce the optimal contraction pattern.” Researchers say the development could lead to a new class of light-based pacemakers and genetically matched tissue patches that replace muscle damaged by a heart attack. They say that, one day, bioengineers may be able to induce pluripotent stem cells fashioned from the recipient's own body or similar cell types that can give rise to genetically matched replacement heart cells paced with light, circumventing the drawbacks of electrical pacemakers. “We might, for instance, create a pacemaker that isn't in physical contact with the heart,” said co-author Dr. Christopher Zarins. “Instead of surgically implanting a device that has electrodes poking into the heart, we would inject these engineered light-sensitive cells into the faulty heart and pace them remotely with light, possibly even from outside of the heart.” In the nearer future, researchers say optogenetics (the combination of genetic and optical methods to control specific events in targeted cells of living tissue) will make it easier to study the heart because they can turn cells on and off with light. Scientists may be able to use these tools to induce disease-like abnormalities and arrhythmias in sample tissues to study how to fix them. They say optogenetics could also lead to advances in various neuronal and cardiac disorders including depression, schizophrenia, cerebral palsy, paralysis, diabetes, pain syndromes and cardiac arrhythmias. For more information, visit: www.stanford.edu