Formation of amyloid in encapsulated human pancreatic and human stem cell-generated beta cell implants

Detection of amyloid in intraportal islet implants of type 1 diabetes patients has been proposed as cause in their functional decline. The present study uses cultured adult human islets devoid of amyloid to examine conditions of its formation. After intraportal injection in patients, amyloid deposits <15 mu m diameter were identified in 5%-12% of beta cell containing aggregates, 3-76 months posttransplant. Such deposits also formed in glucose-controlling islet implants in the kidney of diabetic mice but not in failing implants. Alginate-encapsulated islets formed amyloid during culture when functional, and in all intraperitoneal implants that corrected diabetes in mice, exhibiting larger sizes than in functioning nonencapsulated implants. After intraperitoneal injection in a patient, retrieved single capsules presented amyloid near living beta cells, whereas no amyloid occurred in clustered capsules with dead cells. Amyloid was also demonstrated in functional human stem cell-generated beta cell implants in subcutaneous devices of mice. Deposits up to 35 mu m diameter were localized in beta cell-enriched regions and related to an elevated IAPP over insulin ratio in the newly generated beta cells. Amyloid in device-encapsulated human stem cell-generated beta cell implants marks the formation of a functional beta cell mass but also an imbalance between its activated state and its microenvironment.

Automated summary

The study suggests that the formation of amyloid in intraportal islet implants may contribute to the functional decline in type 1 diabetes patients. Amyloid deposits were found in a small percentage of beta cell-containing aggregates post-transplantation, as well as in glucose-controlling islet implants in diabetic mice. The presence of amyloid in encapsulated islets and stem cell-generated beta cell implants may indicate an imbalance between activated state and microenvironment, affecting the function of the beta cells.