Researchers have developed a technique to implant a thread-like device containing insulin-secreting pancreatic cells under the skin. The device reversed type 1 diabetes in mice without the need for anti-rejection drugs. The device could one day replace insulin injections.
The immune system of people with type 1 diabetes attacks and destroys the insulin-producing cells in the pancreas, known as islet cells, thereby preventing insulin secretion, resulting in patients having to inject insulin or use an insulin pump for life.
Researchers at Cornell University and the University of Alberta have collaborated to create a subcutaneous implant that secretes insulin while avoiding the immune response that implanted devices can produce.
"I've received a lot of emails and requests for help from parents and patients over the years," said Minglin Ma, one of the corresponding authors of the study. "Type 1 diabetes is a very bad disease, and a lot of children suffer from it. So we are really serious about pushing this into clinical applications and into areas of impact."
In 2017, Ma from Cornell University's College of Agriculture and Life Sciences (CALS) developed Alginate Fiber Islet Implantation Cord (TRAFFIC), a detachable nylon thread implant containing hundreds of thousands of islet cells, protected by a thin alginate hydrogel coating, and inserted into the abdominal cavity. In 2021, a more powerful version of the implant became available, effectively controlling blood sugar in mice for up to six months.
The horse implant caught the attention of UC diabetes researcher James Shapiro, who created a method to implant islet cells into subcutaneous channels and then apply immunosuppression to protect them.
Shapiro, another corresponding author on the study, said: "I was interested in the advantages of Ma's approach because it circumvented the need for immunosuppression, and I wondered if we could combine our two innovative strategies to improve cell survival. In fact, it worked! By combining the two, it did improve the skin site of the transplanted cells without the need for anti-rejection drugs."
The result of the collaboration is SHEATH, the subcutaneous host alginate thread.
The SHEATH implantation process is divided into two steps. First, a medical-grade nylon catheter is inserted under the skin and remains there for four to six weeks. Catheters trigger a controlled foreign body inflammatory response, resulting in the formation of a dense network of blood vessels around the catheter. Once the catheter is removed, the alginate-based islet cell seeding device is inserted into the pockets or channels that have been created, and surrounding blood vessels provide the islet cells with the oxygen and nutrients they need.
"This channel is perfect for our equipment," Ma said. Shapiro gave an analogy: "It's like a gloved hand. It's much easier and less invasive to put something under the skin than in the abdomen. It can be done on an outpatient basis, so you don't have to be hospitalized. It can be done under local anesthesia."
Implantation of the SHEATH system into diabetic mice reversed the condition without the need for immunosuppressants. Experiments have shown that this system has a strong ability to reverse diabetes in the long term, with some mice having hyperglycemia corrected for more than 190 days. In addition, the system can remove and replace failed implants based on rising blood sugar levels. After getting the new implant, blood sugar levels returned to normal.
To demonstrate the scalability of the system, the researchers successfully developed procedures for implementing the SHEATH method in mini-pig bodies, including insertion, removal, and replacement of the implant.
The researchers acknowledge that while the SHEATH system's capabilities are promising, more challenges need to be overcome for clinical application. Specifically, acceptable catheter lengths need to be determined and anatomically appropriate implantation sites identified.
"The challenge we face is that it is very difficult to keep these islet cells functional long-term in the body because the device blocks the blood vessels, but native islet cells in the body are known to be in direct contact with blood vessels that provide nutrients and oxygen," Ma said. "The device is designed in a way that allows us to maximize the exchange of large amounts of nutrients and oxygen, but we may need to provide additional means to support long-term function of the cells in large animal models and ultimately in patients."
These 'extras' may include incorporating a continuous supply of oxygen into the equipment. Ma has formed a new Cornell spinout company, PersistaBio, to develop a separate device that delivers extra oxygen to cells.
Despite these challenges, researchers hope that future versions of the implant will last two to five years before needing replacement.
The research was published in the journal Nature Biomedical Engineering.