Given that there are currently 415 million adults around the world with diabetes, it's not surprising there's a multi-billion dollar market for diabetic devices. Although technology has made managing the disease easier, it still involves taking blood samples to determine whether an insulin shot is needed, something that is fraught with complications since glucose levels can fluctuate due to a variety of reasons. But what if there was a way to trigger the body to produce insulin on demand? That's exactly what a team of scientists from China has done by creating a system that uses a smartphone to direct engineered cells to produce insulin when needed.

Led by East China Normal University's Haifeng Ye, the solution is inspired by smart home systems and marries telecommunications technology with two emerging fields of medicine: cell-based therapy and optogenetics, a technique that makes use of light to regulate cellular activity and one that has been used in a variety of novel experiments to restore heart rhythms, reverse blindness and activate predatory instincts in mice.

In this case, optogenetics plays a key role in enabling cells to process smartphone signals. Not only can light be generated by electronic commands, it can also trigger biological processes, such as circadian rhythms and in this case, gene expression. With this principle in mind, the team customized cells with a light-sensitive protein that can create insulin when illuminated by wirelessly powered far-red LEDs (FRLs). Both the lights and cells were then embedded in a soft bio-compatible sheath, which was implanted under the skin of diabetic mice.

The implant with the far-red LED and engineered cells before it's embedded under the skin of a diabetic mouse(Credit: Shanghai Key Laboratory of Regulatory Biology)

In addition to these engineered cells, the system also comprises three other components: an Android-based smartphone app that controls the lights remotely; a control box containing an electromagnetic circuit that activates the lights; and a Bluetooth-enabled blood glucose meter that sends glycemic values to the smartphone app for analysis.

The result is a closed loop system in which the glucose meter is programmed to conduct glucose testing automatically on a periodic basis. The data is then sent to the app, which analyzes it to determine how much insulin is needed before sending a signal to the control box to activate the LED lights so the cells can begin production.

According to the paper, the diabetic mice were exposed to four hours of light each day and the FRL was able to maintain a sustainable level of insulin production for 15 days. Within two hours of irradiation, they were able to reach nondiabetic levels of blood glucose without any hypoglycemic side effects.

For Ye, who has been working on the idea of engineering "a smart insulin-sensor circuit that can sense, monitor and profile insulin levels in the blood stream" since his days as a PhD student at ETH Zurich, this study builds on his early work, which saw him using blue light to control glucose levels in mice. However, as continuous exposure to blue light can be toxic to mammalian cells, the decision was made to develop a "more robust" system using FRLs, which are commonly used in physiotherapy infrared lamps, and a multi-disciplinary approach involving electrical engineering, software engineering, optogenetics and synthetic biology. While diabetes was the focus of this study, the system can also be adapted to treat other metabolic diseases.

That said, although this study can be seen as a successful proof of concept, the authors also acknowledge that there is more work that needs to be done before the technique can be tested on humans. One of the challenges is that the system still requires blood to be drawn manually to trigger the therapeutic response. The current device also requires the mice to be close to the electromagnetic emission circuit, which limits their mobility and exposes them to electromagnetic radiation. Finally, in order for this system to make its way from the lab into the clinic, it will need to be validated in cells derived from the same patients undergoing treatment and integrated with the optogenetic gene circuits.

According to the researchers, one possible way of getting around these limitations is to replace the glucometer with a continuous glucose monitor that would be implanted in the body so that it can monitor blood glucose levels round the clock. And instead of the electromagnetic coil, the LED lights could be powered by clinically approved batteries to allow patients freedom of movement and avoid exposure to electromagnetic radiation. As for testing the technique using patient-derived autologous cells, plans are in the works to test this in hospitals in the future.

The study has been published in Science Translational Medicine.

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