In vivo Studies on Insulin Permeability of an Immunoisolation Device Intended for Islet Transplantation Using the Microdialysis Technique

Abstract

In this study, insulin was injected into Theracyte^TM immunoisolation devices to analyze changes in the permeability of the device over time after implantation. The recovery of insulin was studied after subcutaneous implantation of the devices in rats, using the microdialysis technique. The area under the insulin cocnetration vs. time curves (AUC) after insulin injection in devices implanted 1 day previously did not differ significantly from the AUC after subcutaneous injection. At 1, 2 and 4 weeks after implantation, the recovery of insulin was significantly reduced, but at 3 months, the AUC was not significantly different from that in the control group. Histological examination showed that the number of vascular profiles within 15 μm of the device were significantly higher at 2, 4 weeks and 3 months after transplantation when compared to numbers at 1 week. The design of the device allows transplantation of cells at a chosen time point after its implantation. Delayed filling of the device would allow neovascularization of the device surface before graft implanatation and we suggest that such a schedule might improve function of the encapsulated graft.

Assessment of Immune Isolation of Allogeneic Mouse Pancreatic Progenitor Cells by a Macroencapsulation Device

“…The polymeric membranes have a nominal pore size of 0.45μm and are impermeable to cells. This device is built in a similar planar design and with similar membrane properties as the Theracyte device, 20 but using more modern manufacturing and quality control methods with proper design controls as required for developing a medical device for eventual use in human subjects. Encaptra devices have passed all the biocompatibility tests required by the International Standards Organization and are currently being used in a phase I/II clinical trial (NCT02239354).…”

Redox-Dependent Inflammation in Islet Transplantation Rejection

“…However, the thickness of these capsules can impede the transfer of insulin, oxygen, and other nutrients, potentially harming the islets and limiting possible transplantation sites ( 164 , 165 ). More recently, the development of new technologies including the subcutaneous implantation of islets held within a thin membrane-bound device by TheraCyte can protect insulin-producing cells from the immune system and delay islet allograft rejection ( 166 , 167 ). In addition, a device by ViaCyte utilizing PEC-01 precursor insulin-producing cells and a subcutaneous transplantation site is currently in a phase 1 clinical trial.…”

Development of an encapsulated stem cell-based therapy for diabetes

“…However, the curative dose of transplanted macroencapsulated islets to reverse diabetes in preclinical models was 10 times higher than the curative dose of non-encapsulated islets, mainly due to the lack of sufficient vascularization of the freshly implanted device and to transport limitations 26 . In addition to transport limitations, macrodevices like the Theracyte device generally induced heavy fibrotic responses at the device-host interface 27, 28 . To minimize host responses, the Theracyte device has been modified by Viacyte into the Encaptra® Drug Delivery System.…”