Sensors detect dead transplanted cells

Researchers have devised tiny sensors to detect whether cells transplanted into a living animal are alive or dead.

The innovation can help doctors determine when and why such transplants fail, speeding the development of effective cell replacement therapies for conditions such as liver failure and type 1 diabetes, the researchers say.

“This should take a lot of the guesswork out of cell transplantation by letting doctors see whether the cells survive, and if not, when they die,” study leader Kannie Chan says. “That way, they may be able to figure out what’s killing the cells, and how to prevent it.”

Regenerative medicine depends on reliable means of replacing damaged or missing cells, such as injecting pancreatic cells into people with diabetes whose own cells don’t make enough insulin.

Reported in Nature Materials, the study combined nanoscale acidity sensors and magnetic resonance imaging to tell if liver cells injected into mice survived over time.

“This technology has the potential to turn the human body into less of a black box and tell us if transplanted cells are still alive,” says senior author Mike McMahon, associate professor of radiology at the Johns Hopkins University School of Medicine. “That information will be invaluable in fine-tuning therapies.”

Will they survive?

To protect the transplanted cells from the immune system, while allowing the free flow of nutrients and insulin between the cells and the body, they can be encased in squishy hydrogel membranes before transplantation. But, explains McMahon, “once you put the cells in, you really have no idea how long they survive.”

Such transplanted cells eventually stop working in most patients, who must resume taking insulin. At that point, physicians can only assume that cells have died, but they don’t know when or why, McMahon says.

With that problem in mind, McMahon’s group, which specializes in methods of detecting chemical changes, collaborated with the research group headed by Jeff Bulte, director of cellular imaging at the Institute for Cell Engineering. Bulte’s group devises ways of tracking implanted cells through the body using MRI.

Very tiny sensor

Led by Chan, a research fellow, the team devised a nanoscale sensor—that is, one so small it can be measured in billionths of a meter. The sensor consists of a thin outer layer of fat filled with L-arginine, a nutritional supplement that responds chemically to small changes in acidity (pH) caused by the death of nearby cells, giving off a signal that can be detected by MRI.

To test how these nanosensors would work in a living body, the team loaded them into hydrogel spheres along with liver cells—a potential therapy for patients with liver failure—and another sensor that gives off bioluminescent light only while the cells are alive. The spheres were injected just under the skin of mice. The MRI accurately detected where the cells were in the body and what proportion was still alive.

The light indicators cannot be used in humans because our bodies are too large for visible signals to get through. But for the purposes of the study, they allowed the team to double check if the MRI nanosensors were working properly in the mice.

“It was exciting to see that this works so well in a living body,” Chan says. The team hopes that because the components of the system—hydrogel membrane, fat molecules, and L-arginine—are safe for humans, adapting their discovery for clinical use will prove relatively straightforward.

Potential applications of the sensors are not limited to cells inside hydrogel capsules, Bulte notes. “These nanoparticles would work outside capsules, and they could be paired with many different kinds of cells. For example, they may be used to see whether tumor cells are dying in response to chemotherapy,” he says.

The National Institute of Biomedical Imaging and Bioengineering funded the study.

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