A novel endovascular bioartificial pancreas device to treat type 1 diabetes
Sara Photiadis1, Khanh Hoa Nguyen1, Quynh Mai1, Gabriel Montanez1.
1Isla Technologies, Inc., San Carlos, CA, United States
Previous research and rationale Type 1 diabetes (T1D) (1, 2) is an autoimmune disease that causes destruction of insulin-producing beta-cells within the islets of Langerhans in the pancreas. Bioartificial pancreas (BAP) devices with immune-protecting barriers for islet transplantation are an emerging T1D treatment strategy (3-7), but these devices remain challenging to implement due to (i) poor islet graft survival in low oxygen subcutaneous environments and (ii) suboptimal transport glucose and insulin for metabolic control (8-15).
Isla Technologies’ (Isla) T1D treatment strategy is an endovascular BAP (eBAP) device, which overcomes existing challenges in immunoisolation (16, 17) and hypoxia-induced islet death (18) through a novel approach of delivering islets within immune-protective membranes on a stent scaffold to a peripheral artery. The eBAP device leverages the artery’s (i) higher oxygen environment and (ii) blood flow to improve diffusion of glucose and insulin through the device (19). To demonstrate feasibility, we implanted the eBAP into a non-diabetic swine model without immunosuppression.
Methods Non-diabetic, 70 Kg Yorkshire swine (N=5) were implanted with eBAP devices without immunosuppression. Group 1 received the eBAP device with sterile alginate alone (N=2). Group 2 received the eBAP device with sterile alginate and 50,000 juvenile porcine islet equivalents (N=3). The devices were implanted using a 20 Fr catheter through the femoral artery to the infrarenal aorta. Angiograms were obtained over 1 month to evaluate the formation of blood clots and explanted devices were histologically examined for islet endocrine markers and viability.
Results We achieved 100% patency in all control devices and devices with islets. In Figure 1, the angiograms on panel A represent day 0 and on panel B, day 30 for an implant with islets. Explanted islet-containing devices at day 30 were evaluated for gross and microscopic histopathology. In Figure 1C, the blood contacting surface of the device is shown, indicating minimal inflammatory response. The histological sections show positive staining with antibodies against human insulin and glucagon and lack of caspase 3 staining in islets. (Figure 1D).
Conclusion We show 30-day safety data of a novel eBAP device delivered endovascularly to a peripheral artery in non-diabetic swine without immunosuppression. The eBAP device with and without allogeneic islets showed no evidence of thrombosis over 30 days and histopathology indicated endocrine functionality and viability of the islets. Further investigation is warranted to test the ability of the eBAP device to reverse diabetes in vivo and to assess its extended safety profile.
Thomas Krebs. Alice Tomei. Jonathan Lakey.
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Lectures by Sara Photiadis
| When | Session | Talk Title | Room |
|---|---|---|---|
|
Sat-28 14:00 - 15:30 |
Encapsulation of cellular transplants 1 | A novel endovascular bioartificial pancreas device to treat type 1 diabetes | Indigo D |