The Medical Technology Blog

This weeks artice on the Medical Technology Blog is taken fromEspicom’s business publication, Cardiovascular Device Business, please read on…

In a paper published in the September issue of the Biophysical Journal, lead author Dr Oscar Abilez, a postdoctoral scholar and PhD candidate in bioengineering, and a multidisciplinary team from Stanford University, describe how they have, for the first time, engineered human heart cells that can be paced with light using a technology called optogenetics. In the near term, the researchers say the advance will provide new insight into heart function. In the long term, however, the development could lead to an era of light-based pacemakers and genetically matched tissue patches that replace muscle damaged by a heart attack.

To create the light-responsive heart cells, the researchers first inserted DNA encoding a light-sensitive protein called channelrhodopsin-2 (ChR2), into human embryonic stem cells. ChR2 controls the flow of electrically charged ions into the cell. For heart cells, the primary ion is sodium, which initiates an electrochemical cascade that causes the cell to contract. They then transformed the optogenetically engineered stem cells into cardiomyocytes those that respond to light.

The key 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. After creating the cells in a laboratory dish, the researchers tested 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. With these models, the researchers say they can demonstrate not only that pacing cells with light will work, but also where to best inject cells to produce the optimal contraction pattern.

The long-term goal is the development of a new class of pacemakers. At present, surgically-implanted electrical pacemakers and defibrillators are commonplace, regulating the pulses of millions of faulty hearts around the world. However, Abilez adds that neither is without problems – pacemakers fail mechanically and the electrodes can cause tissue damage. Defibrillators, on the other hand, can produce tissue damage due to the large electrical impulses that are sometimes needed to restore the heart’s normal rhythm. In the future, the researchers envision that bioengineers will use induced 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.

Co-author, Dr Christopher Zarins, professor emeritus of surgery and director of the lab, speculates the the work could result in a pacemaker that is not in physical contact with the heart. Instead of surgically implanting a device that has electrodes poking into the heart, engineered light-sensitive cells would be injected into the faulty heart and used to pace the heart remotely with light, possibly even from outside of the heart. The leads for such a light-based pacemaker might be placed outside the heart, but inside the pericardium, the protective sack surrounding the heart. Another concept to be explored is a pacemaker placed inside the heart chambers, as with traditional pacemakers, whose light can travel through the intervening blood to pace light-sensitive heart cells implanted inside. Since the new heart cells are created from the host’s own stem cells, they would be a perfect genetic match.

The authors conclude that optogenetics could also lead to advances beyond the heart. It might lead to new insights for various neuronal, musculoskeletal, pancreatic and cardiac disorders, including depression, schizophrenia, cerebral palsy, paralysis, diabetes, pain syndromes and cardiac arrhythmias.

Espicom Business Intelligence

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