Imagine taking out your smartphone and asking, “Can you control my blood sugar now?” Ideally, you wouldn’t even have to ask—if the smartphone were part of a loop that wirelessly connected your glucometer and an implanted population of cells engineered to secrete insulin on demand.
Such a setup, assembled by scientists based at the Shanghai Key Laboratory of Regulatory Biology, was recently shown to keep blood sugar levels within normal limits in diabetic mice. Details of this work, a synthetic biology tour de force, appeared April 26 in the journal Science Translational Medicine, in an article entitled “Smartphone-Controlled Optogenetically Engineered Cells Enable Semiautomatic Glucose Homeostasis in Diabetic Mice.”
“Using a multidisciplinary design principle coupling electrical engineering, software development, and synthetic biology, we have engineered a technological infrastructure enabling the smartphone-assisted semiautomatic treatment of diabetes in mice,” wrote the article’s authors. “A custom-designed home server SmartController was programmed to process wireless signals, enabling a smartphone to regulate hormone production by optically engineered cells implanted in diabetic mice via a far-red light (FRL)–responsive optogenetic interface.”
Essentially, the researchers added the cells to a soft biocompatible sheath that also contained wirelessly powered red LED lights to create HydrogeLEDs that could be turned on and off by an external electromagnetic field. Implanting the HydrogeLEDs into the skin of diabetic mice allowed the researchers to administer insulin doses remotely through a smartphone application. When the cells in the hydrogel were stimulated by the red LED lights, they produced a short variant of human glucagon-like peptide 1 (shGLP-1) or mouse insulin.
The scientists, led by Haifeng Ye, Ph.D., not only custom-coded the smartphone control algorithms, but also designed the engineered cells to produce insulin without any “cross-talk” between normal cellular signaling processes. The scientists went on to pair the system with a Bluetooth-enabled blood glucose meter, creating instant feedback between the therapeutic cells and the diagnostic device that helped diabetic animals rapidly achieve and maintain stable blood glucose levels in a small pilot experiment over a period of several weeks.
“In vivo production of shGLP-1 or mouse insulin by the engineered cells in the hydrogel could be remotely controlled by smartphone programs or a custom-engineered Bluetooth-active glucometer in a semiautomatic, glucose-dependent manner,” the authors continued. “By combining electronic device–generated digital signals with optogenetically engineered cells, this study provides a step toward translating cell-based therapies into the clinic.”