Researchers have developed a technique to implant thread-like devices containing insulin-secreting pancreatic cells under the skin. The device reversed type 1 diabetes in mice without the need for anti-rejection medications. Someday, this device could replace insulin injections.
The immune system in people with type 1 diabetes attacks and destroys the insulin-producing cells in the pancreas, known as the islet cells, thus blocking the secretion of insulin, resulting in the patient having to inject insulin or use an insulin pump for the rest of their lives.
Researchers at Cornell University and the University of Alberta have collaborated to create a subcutaneous implant that both secretes insulin and avoids the immune response that the implanted device may generate.
Ma Minglin, one of the corresponding authors of the study, said:"Over the years, I've received a lot of emails and requests for help from parents and patients that type 1 diabetes is a very bad condition and a lot of children suffer from it. So we're really serious about taking it to the clinic, to the impactful field. "
In 2017, the MA of Cornell University's College of Agriculture and Life Sciences (CALS) developed:"The islets are implanted with alginate fiber threads"(traffic), which is a removable nylon thread implant containing hundreds of thousands of pancreatic islet cells, protected by a thin alginate hydrogel coating, and inserted into the abdominal cavity. In 2021, a more powerful version of the implant was introduced, which was effective in controlling blood sugar in mice for up to six months.
The horse's implant caught the attention of James Shapiro, a diabetes researcher at the University of California in the United States, who created a method to implant pancreatic islet cells into the subcutaneous channel and then apply immunosuppression to protect them.
Shapiro, another corresponding author of the study, said:"I was intrigued by the merits of MA's approach because it avoids the need for immunosuppression, and I wondered if we could combine our two innovative strategies to improve cell viability. In fact, it worked!By combining the two, it does improve the site of transplanted cells without the use of anti-rejection medications. "
The result of this collaboration is the sheath, the subcutaneous host alginate line.
The Sheath implantation process is a two-step process. First, a medical nylon catheter is inserted under the skin and left under the skin for four to six weeks. The catheter triggers a controlled response of foreign body inflammation, resulting in the formation of a dense network of blood vessels around the catheter. Once the catheter is removed, an alginate-based islet cell seeding device is inserted into the pocket or channel that has formed, and the surrounding blood vessels provide the islet cells with the oxygen and nutrients they need.
This passage is perfect for our equipment"Ma said. Shapiro made an analogy:"It's like a gloved hand. It's much easier to put something under the skin than it is in the abdomen, and it's much less traumatic. It can be done on an outpatient basis, so you don't have to stay in the hospital. It can be done under local anesthesia"。
After implantation of the Sheath system in diabetic mice, the condition was reversed without the use of immunosuppressants. Experiments have shown that the system has a powerful ability to reverse diabetes in the long term, and some mice have been corrected for hyperglycemia for more than 190 days. In addition, the system can remove and replace failed implants based on an increase in blood sugar levels. After the new implant was replaced, the blood sugar level returned to normal.
To confirm the scalability of the system, the investigators successfully developed a procedure to implement the Sheath method in mini pigs, including implant insertion, removal, and replacement.
The researchers admit that although the functionality of the Sheath system is promising, there are more challenges to overcome in terms of clinical application. Specifically, an acceptable catheter length needs to be determined, and an anatomically appropriate implant site needs to be determined.
ma said:"The challenge is that it is very difficult to keep these islet cells functional in the body for a long time because the device can block the blood vessels, but it is well known that the native islet cells in the body are in direct contact with the blood vessels that provide nutrients and oxygen. The device is designed in such a way that we can maximize the large exchange of nutrients and oxygen, but we may need to provide additional means to support the long-term function of cells in large animal models and ultimately patients. "
these'Additional means'This may include the addition of continuous oxygen to the device**. MA has formed a new Cornell spin-off, Persista Bio, to develop a separate device to provide additional oxygen to the cells.
Despite these challenges, the researchers hope that future versions of the implant will last for two to five years before they need to be replaced.
The study was published in the journal Nature Biomedical Engineering.