Improved islet encapsulation device for the treatment of type 1 diabetes [PreClinical]

1. A device for islet transplantation for type 1 diabetes was designed and demonstrated to be safe and retrievable in animal models.

2. When tested in mice and dogs, this device successfully reduced glucose levels.

Evidence Rating Level: 2 (Good)

Study Rundown: Type 1 diabetes is an autoimmune condition that attacks pancreatic islets, preventing successful insulin secretion and glucose control. Currently, this condition is managed through daily insulin injections. However, islet transplantation would provide a better and longer-lasting treatment of this condition. The development of a functional islet cell encapsulation device that does not require immunosuppressants or damage cells has, as of yet, proven challenging. Recently, researchers at Cornell University made significant progress in the development of such a device.

These researchers call their device TRAFFIC, or thread-reinforced alginate fiber for islet encapsulation. Rat islets are encapsulated in an alginate hydrogel, which is necessary to prevent immune rejection by the host. The hydrogel containing the rat islets surrounds a polymer thread to form a cylindrical device. When this device was transplanted into normal and diabetic mice, the blood glucose levels of diabetic mice was reduced, and the mice remained normoglycemic for 4 weeks. Additionally, no significant tissue damage, fibrosis, or cellular overgrowth was noted on the device or peritoneum of these mice. Subsequently, human islets were transplanted into immunodeficient diabetic mice with similar results to the rat islet studies. Finally, TRAFFIC was implanted into two dogs. Following implantation, the islets were found to be functional and resulted in no significant damage or inflammation.

This study is one of the first to outline the development of an effective and retrievable therapy involving islet transplantation for type 1 diabetes. However, the in vivo efficacy of this device in humans, the number of islets needed for successful treatment, and the length of time this device needs to stay implanted for long term success in humans are all variables that need to be assessed. Despite the unknowns, these initial analyses provide great promise for an improved treatment for type 1 diabetes.

Click to read the study in PNAS

Relevant Reading: Beta-cell replacement strategies for diabetes

In-Depth [animal study]: To create a nanoporous and durable thread, a coated nylon suture was twisted into a 4-strand thread and cross-linked with CaCl2. An alginate hydrogel solution was molded and formed around the thread. TRAFFIC was then implanted into the peritoneal cavity of immunocompetent mice and the device was analyzed 2 weeks and 7 months following implantation. Little cellular overgrowth or fibrosis were found using microscopy, photography, and H&E staining demonstrating biocompatibility of the device. Cell viability of the encompassed islets was next assessed through exposure of the islets to solutions with varying glucose concentrations and assessing the concentration changes of glucose and insulin over time. It was confirmed that the islets were responding to the change in glucose levels through increasing insulin secretion.

The ability of this device to correct diabetes in mice was then tested by transplanting the TRAFFIC device, containing around 475 rat islets, into mice induced with diabetes through the administration of 50 mg/kg streptozocin (STZ). The blood glucose levels of diabetic mice reduced to normal range within 2 days and were maintained for 4 weeks following removal (p< 0.05). Similar results demonstrating effective glucose control and insulin secretion were obtained when TRAFFIC, containing human islets, was implanted into STZ-induced diabetic, immunodeficient, SCID-beige mice.

Finally, TRAFFIC functionality and safety was ultimately tested in two dogs. TRAFFIC was laparoscopically implanted near the liver of these dogs and led to little fibrosis on the device and tissue containing the implant. The islets in the implant were found to be functional following implantation resulting in no significant increase in adverse immune reactions as assessed through blood work involving white blood cell counts and quantification of liver enzymes.

Image: PD

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