Type 1 diabetes (T1D) is an autoimmune disease in which the immune system destroys insulin-producing beta cells in the pancreas. Currently, approximately 1.4 million people are living with T1D in the United States, and this number is projected to increase to more than 2 million by 2040.1 Without insulin, the body cannot regulate blood sugar levels, and many people with T1D require lifelong insulin injections.
An alternative T1D treatment is clinical islet transplantation (CIT). In this transplant, islets containing beta cells from a donor enter the patient’s circulation through the portal vein and are ultimately transplanted into the liver. Although CIT has shown promising results, several challenges remain, including patients having to undergo immunosuppressive therapy to avoid transplant rejection, which can lead to opportunistic infections and organ toxicity.2 To avoid administering immunosuppressive drugs, researchers have considered transplanting beta cells encapsulated in substances that physically block immune cell attacks. However, these strategies often create a hypoxic environment that is harmful to the cells inside. 2
Recent studies have been published to overcome these challenges. nature communications Alessandro Grattoni and his colleagues at Houston Methodist Research Institute offer a new approach to treating diabetes through islet therapy. They developed a 3D-printed implantable device, named Neoangiogenic Implantable Cell Homing and Encapsulation (NICHE), that allows blood vessels to permeate and oxygenate encapsulated beta cells. was developed.3
Grattoni’s device contains a central reservoir that holds beta cells and a mesenchymal stem cell (MSC) hydrogel that induces angiogenesis within the NICHE. A U-shaped reservoir containing immunosuppressants surrounds the cells once implanted, protecting them from immune responses.
“There are several advantages to using the device,” said Minglin Ma, a professor at Cornell University who was not involved in the study. You can.”
The researchers first tested NICHE’s ability to release drug from a U-shaped reservoir and allow angiogenesis within the central reservoir in vitro and in rats with the device implanted subcutaneously. “We were able to obtain vascularization that guarantees a higher oxygen level than is required for islet transplantation, meaning blood vessels are entering the inside of the device from the outside,” Grattoni said. said.
There are several advantages to using the device. Cells can be bound at localized sites, allowing immunosuppressive drugs to be administered locally.
Grattoni and his team then tested NICHE subcutaneously in immunocompetent rats that became diabetic. After transplantation, the researchers divided the rats into groups based on the type of immunosuppression they experienced. Some rats received locally released drug from NICHE, others received systemic injections of immunosuppressants, and a third control group received no drug. After monitoring the rats for more than 150 days, the researchers found that diabetic rats treated with locally or systemically administered immunosuppressive drugs had significant effects compared to control rats, including significantly lower blood sugar levels within 10 days after transplantation. It was determined that there had been an improvement. We also observed fewer cytotoxic T cells and macrophages in the NICHE device in the drug treatment group.
Furthermore, the researchers confirmed that local and systemic immunosuppression caused similar amounts of angiogenesis and limited immune cell infiltration within the device. However, local immunosuppression reduced drug accumulation in organs such as kidney and liver compared to rats receiving systemic treatment, limiting the potential for drug toxicity. “We knew he was very excited about two things: first, using this device to achieve euglycemia; and second, being able to locally trap this suppressor. ,” Grattoni said.
To see how the device would work in non-human primates, Grattoni and colleagues also implanted the rat-sized NICHE device into cynomolgus monkeys. Similar to rats, the implanted devices were extensively vascularized, allowing beta cell survival within the device.
Grattoni is excited about the future of his device. He received a Ph.D. Additional funding received. His team is currently evaluating the optimal cocktail of immunosuppressive drugs to use on larger cellular reservoirs.
References
- Centers for Disease Control and Prevention, “National Diabetes Statistics Report, 2020,” Atlanta, Georgia: U.S. Department of Health and Human Services Centers for Disease Control and Prevention2020.
- J. Paez-Mayorga et al., “A new strategy of beta cell transplantation for the treatment of diabetes.” Trend Pharmacy Science, 43:221-33, 2022. Doi: 10.1016/j.tips.2021.11.007
- J. Paez-Mayorga et al., “Transplantable niche with local immunosuppression for islet allotransplantation achieves reversal of type 1 diabetes in rats.” Nat Commune, 13:795, 2022. Doi: 10.1038/s41467-022-35629-z