A coin-sized implantable device created by scientists at Houston Methodist Research Institute Department of Nanomedicine could drastically alter the course of treatment for type 1 diabetes (T1D). The team, headed by Alessandro Grattoni, PhD, chair of the department of nanomedicine, delivered islet cells and immunotherapy directly into the 3D printed neovascularized implantable cell homing and encapsulation (NICHE) device, which they described as akin to a bioengineered pancreas. When tested in animal models, the NICHE implants restored healthy glucose levels and eliminated T1D symptoms for more than 150 days, while avoiding severe adverse effects of anti-rejection therapy by administering immunosuppressive drugs only where the transplanted islet cells were located.

Reporting on their development in Nature Communications (“Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal in rats,” corresponding author Grattoni and colleagues stated, “Overall, the NICHE is a promising solution with the potential to transform the field of islet transplantation for safe and prolonged treatment of type 1 diabetes.” The researchers hope that with further developments, clinical trials could start in three years.

Type 1 diabetes is caused by an autoimmune reaction that destroys the pancreatic islet cells that produce insulin. It can also cause kidney failure. Daily insulin injections are the most conventional treatment for T1D, but attaining tight control of glucose levels remains challenging and cumbersome for patients. Further, in more severe cases, patients may need pancreas and kidney transplants, or they may qualify for an islet cell transplant—clinical pancreatic islet transplantation (CIT)—through which the islet cells of a deceased pancreas donor are harvested, processed, and then transplanted into the T1D’s patient’s liver. “In CIT, isolated islets are transplanted into the portal circulation and engraft passively in hepatic sinusoids,” the authors explained. “As pancreatic islets provide dynamic glucose control, CIT significantly improves glycemic profile, decreases hypoglycemic events, and reduces progression of diabetes-related comorbidities.”

However, while such transplants can help to improve a patient’s symptoms, as with all organ transplants, one of the biggest challenges is the need for lifelong immunosuppressive drugs to avoid transplant rejection. Lifelong immunosuppression can lead to patients being vulnerable to infectious diseases and increases the risk of certain types of cancer. Hypoxia-related graft attrition is another key challenge, the authors reported. “Pancreatic islet transplantation efficacy for T1D management is limited by hypoxia-related graft attrition and need for systemic immunosuppression.”

Grattoni’s nanomedicine lab at Houston Methodist focuses on implantable nanofluidics-based platforms for controlled and long-term drug delivery and cell transplantation to treat chronic diseases. Their newly described flat, coin-sized NICHE device, placed under the skin, comprises a cell reservoir for the islets and a surrounding drug reservoir for localized immunosuppressive therapy. The device was developed to meet key criteria for long-term islet engraftment and therapeutic effect. These include “islet accessibility to oxygen, nutrients, and metabolic products to maintain function, immune system evasion to prevent rejection, and reduced footprint and invasiveness to improve translatability and patient acceptability,” the scientists wrote. The resulting platform is, they claim, the first to combine direct vascularization and local immunosuppression into a single, implantable device for allogeneic islet transplantation and long-term T1D management. Direct vascularization is fundamental for supplying nutrients and oxygen for maintaining the viability of transplanted islet cells.

“Vascularization of the NICHE central cell reservoir is achieved by leveraging the pro- angiogenic properties of a mesenchymal stem cell (MSC) hydrogel, while integration of an interconnected outer drug reservoir permits direct and local immunosuppressant delivery into the cell reservoir through a nanoporous membrane,” they further explained. The team’s experiments confirmed that localized immunosuppression prevented islet rejection without inducing systemic immunosuppression.

Tests with the device in animal models demonstrated that allogeneic islets transplanted within pre-vascularized NICHE devices engrafted, revascularized, were functional, and reverted diabetes in rats for over 150 days. “Notably, we confirmed that localized immunosuppression prevented islet rejection without inducing toxicity or systemic immunosuppression,” the scientists stated. “A key result of our research is that local immunosuppression for cell transplantation is effective,” added Grattoni. “This device could change the paradigm of how patients are managed and can have a massive impact on treatment efficacy and improvement of patients’ quality of life.”

The NICHE incorporates ports so that drugs can be refilled as needed. The ability to refill the NICHE technology allows for long-term use in patients. In their reported study, the researchers refilled the drug reservoirs every 28 days, which is comparable to other long-acting drugs clinically available for migraine prevention or HIV treatment, they stated. Grattoni’s team is working on scaling up the NICHE technology for clinical deployment, for which drug refilling may only be needed once every six months. Further, changes in drug formulations or concentration could extend refill intervals to once each year, aligning with routine physician visits.

Grattoni and his collaborators aim to expand their research over the next few years, with the goal of testing the NICHE’s safety in humans in about three years.

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