Could “cyborg” transplants replace pancreatic tissue damaged by diabetes?

(Press-News.org) PHILADELPHIA— A new electronic implant system can help lab‑grown pancreatic cells mature and function properly, potentially providing a basis for novel, cell-based therapies for diabetes. The approach, developed by researchers at the Perelman School of Medicine at the University of Pennsylvania and the School of Engineering and Applied Sciences at Harvard University, incorporates an ultrathin mesh of conductive wires into growing pancreatic tissue, according to a study published today in Science.

 

“The words ‘bionic’, ‘cybernetic’, ‘cyborg’, all of those apply to the device we’ve created,” said Juan Alvarez, PhD, an assistant professor of Cell and Developmental Biology. While these terms may sound futuristic, he noted this approach is already in use in the form of deep brain stimulation, which treats neurological conditions. “What we’re doing is like deep stimulation for the pancreas. Just like pacemakers help the heart keep rhythm, controlled electrical pulses can help pancreatic cells develop and function the way they’re supposed to,” he said. 

 

The growing pains of lab-grown pancreatic tissue

In Type 1 diabetes, the immune system mistakenly attacks clusters of hormone-secreting cells called islets, destroying their ability to make the blood-sugar lowering signal insulin. The U.S. Centers for Disease Control and Prevention (CDC) estimates that in 2021 about two million Americans of all ages had this condition. In the most serious cases of Type 1 diabetes, and occasionally Type 2 diabetes, patients need to replace the lost and damaged cells — either with a whole pancreas, segments of it, or islet cells by themselves.

All of these options are often in short supply, forcing patients to wait a year or more for either a pancreas or islet cell transplant. After the procedure, they must take immunosuppressant drugs their entire lives to ensure that their bodies don’t reject the transplant. However, pancreatic tissue grown in the lab doesn't present these drawbacks.

Researchers in Alvarez’s lab partnered with the Jia Liu lab at Harvard University to implant a fine, electrically conductive mesh into pieces of developing pancreatic tissue, capable of detecting the electrical signals from the islet cells. They then introduced a natural, 24-hour rhythm in electrical activity, prompting the cells to mature and respond properly to sugar — overcoming a major challenge to growing fully functional pancreatic tissue outside the body. Such alternative transplants promise to dramatically expand the supply of new tissue and, if engineered properly, reduce the risk of rejection. 

This approach of coaxing human stem cells to produce beta and other hormone secreting cells is already being tested in clinical trials. Still, a key challenge remained: even with this electrical boost, the lab-grown cells often don’t fully mature and may not release insulin and other hormones as reliably as natural ones.

Putting cells on a schedule

Alvarez and co-senior author Jia Liu, PhD, set out to understand how the cells could become able to fulfill their calling. “I like to call it when cells get their PhDs,” Alvarez said. “It is when cells stop being undecided undergrads, and commit to their career path of being pancreatic or islet cells.”

Alvarez’s lab specializes in growing three-dimensional pieces of pancreatic tissue called organoids, while Liu’s lab develops tissue-like electronic implants. To create the cyborg tissue, they placed a stretchable mesh- thinner than a piece of human hair- between layers of cells, which then clustered together to form islets. This set up allowed the team to record the electrical activity of individual islet cells over two months, and gain new insight into this transition, including the role of circadian rhythms. 

In previous research, Alvarez’s lab showed that exposing functionally immature cells to a circadian rhythm — like the body’s natural 24-hour internal clock that regulates the sleep-wake cycle, digestion, and other systems  — prompts the cells fully develop into their mature, specialized roles. The team found that after four days, the cells continued cycling on their own.

This new rhythm prompted the islet cells to mature so that they secreted hormones at the right times. The data, meanwhile, showed that not only did the initial cycles teach individual cells new electrical behavior, but it seemed to help the cells start working in sync with each other, like a coordinated team,  Alvarez said. 

Monitoring “cyborg” pancreatic tissue in real-time with AI 

Alvarez foresees two ways this research could lead to transplant alternatives. Perhaps lab-grown islet cells could be “zapped” to prepare them to go into a patient, then left on their own to produce, store, and release insulin. Or, maybe the mesh could be left in place to monitor and stimulate islet cells. This approach could ensure the cells don’t regress and so stop responding to insulin, as can happen with stress or disease. 

Eventually, AI could control such a system, monitoring the cells and stimulating them when needed. “In the future, we could have a system that runs without human intervention,” Alvarez said. 

This work was supported by the National Institutes of Health (NIDDK DP1DK130673; Human Islet Research Network U24DK104162; NIGMS R35GM157320), Breakthrough T1D (IN0-15 2025-1707-A-N), and a pilot award from the Diabetes Research Center at the University of Pennsylvania (P30DK19525). Additional support was provided through grants from the JDRF (COE-2020-967-M-N) and the JPB Foundation (award no. 1094).

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System (UPHS) and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.

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