Living biomarker using epidermal stem cells developed — Inflammatory areas emit light

Conventional biomarker testing has primarily relied on invasive, single-occasion methods such as blood sampling, while wearable devices have been limited to information from bodily fluids that exit the body, such as sweat and interstitial fluid. A research group led by Distinguished Professor Hiroyuki Fujita from Tokyo City University (Professor Emeritus, the University of Tokyo), Project Professor Shoji Takeuchi and Project Assistant Professor Jun Sawayama (at the time of research) from the Institute of Industrial Science, the University of Tokyo, Team Leader Takashi Tsuji (at the time of research) from the RIKEN Center for Biosystems Dynamics Research (BDR), and Researcher Koji Yano at Canon Medical Systems Corporation Advanced Research Laboratory, has developed a living sensor display using the skin that senses specific biomarkers and expresses fluorescent proteins. Their research was published in Nature Communications.

Cells within living organisms can be considered the ultimate sensors, having the inherent ability to detect chemical substances and inflammatory signals with high sensitivity and selectivity and respond through gene expression via molecular signal pathways. Moreover, the skin has a large surface area, and because epidermal stem cells are located at a shallow depth of 0.1 to 0.3 millimeters from the surface, changes in these cells can be easily detected from the outside.

The research group engrafted skin cultured from cells that emit fluorescence when inflammation occurs in the body onto mouse skin. When inflammatory substances were administered to these mice, the fluorescence intensity of the transplanted area increased, demonstrating that inflammatory conditions within the body could be non-invasively monitored through fluorescence observation from the skin surface. Furthermore, it was confirmed that this sensor function was consistently maintained even through skin metabolism, suggesting that long-term use is possible without maintenance.

The tissue-engineered skin with sensor functionality was created by first introducing genes into human-derived epidermal stem cells so that EGFP would be expressed when inflammatory substances bind and the NF-κB pathway is activated. This tissue-engineered skin showed increased fluorescence intensity through EGFP expression within 24 hours in response to the concentration of inflammatory substances, with a response range of 0 to 20 nanograms per milliliter.

This tissue-engineered skin was transplanted onto the dorsal skin of immunodeficient mice, and engraftment was observed. Tissue observation after four weeks revealed that skin with human-like papillary structures, distinct from the surrounding mouse skin, had formed at the transplant site. Although the area of the transplanted region decreased until 30 days post-transplantation, its size and position remained nearly constant for over 200 days thereafter.

These results demonstrate that by utilizing skin tissue containing stem cells as both a sensor and display device, long-term, non-invasive monitoring of minute biomarkers within the body-which was previously difficult-can be achieved. By modifying the target receptors or sequences, it may be possible to expand this to designable biosensors that detect various molecules other than inflammatory substances (such as hormones and metabolites).

Furthermore, this development will not only greatly improve patient QOL in the management of chronic diseases and preventive medicine against pre-disease states, but is also expected to be applied as a new tool for monitoring the health status of pets and livestock that have difficulty communicating their physical conditions verbally, demonstrating its potential as a "living sensor display" that functions long-term with a single transplantation.

Fujita commented: "The inspiration for this research came to me while listening to a lecture on 'Regenerative Medicine for Everyone' by my fellow researcher, Professor Takashi Tsuji. I glimpsed a 'possible future' where living cells could be transformed into sensors for information within the body, and just by looking at them, you could tell if someone had fallen ill. After eight years of painstaking effort since beginning this research at the Canon Medical Systems Corporation Advanced Research Laboratory, where I was affiliated at the time, we finally published the paper by bringing together the full strength of a wonderful team. Our dream grows with the possibility that this could lead to technology that allows anyone, anywhere, at any time, to observe the health status of animals and humans without harming the body. Of course, careful consideration is necessary, including compliance with ethics and discussions to gain societal acceptance."

Journal Information
Publication: Nature Communications
Title: Living sensor display implanted on skin for long-term biomarker monitoring
DOI: 10.1038/s41467-025-67384-2