Oxygen-permeable microwell device maintains islet mass and integrity during shipping

Abstract

Islet transplantation is currently the only minimally invasive therapy available for patients with type 1 diabetes that can lead to insulin independence; however, it is limited to only a small number of patients. Although clinical procedures have improved in the isolation and culture of islets, a large number of islets are still lost in the pre-transplant period, limiting the success of this treatment. Moreover, current practice includes islets being prepared at specialized centers, which are sometimes remote to the transplant location. Thus, a critical point of intervention to maintain the quality and quantity of isolated islets is during transportation between isolation centers and the transplanting hospitals, during which 20–40% of functional islets can be lost. The current study investigated the use of an oxygen-permeable PDMS microwell device for long-distance transportation of isolated islets. We demonstrate that the microwell device protected islets from aggregation during transport, maintaining viability and average islet size during shipping.

Porous microwell scaffolds for 3D culture of pancreatic beta cells to promote cell aggregation and insulin secretion

“…41,42 The porous structure of a microwell scaffold could allow free permeation of oxygen and nutrients that are important for maintaining cell viability by alleviating hypoxia stress, importing glucose and secreting insulin. 43,44…”

Microwell culture platform maintains viability and mass of human pancreatic islets

“…Previous literature demonstrated that microwells ~400 µm in diameter maintained functional human islets for 7 days ( 46 ). Another study showed that 500 µm-microwells effectively segregated islets for the short-term, with a shaking culture condition mimicking islet shipping ( 47 ); however, multiple islets in a well were observed, which indicates the importance of islet-size-specific microwells. We addressed the issue by preparing different-sized microwells, minimizing the fusion of large islets with a simple and practical approach.…”

Type 1 diabetes and engineering enhanced islet transplantation

“…For instance, Jiang et al [330] incorporated 0.1 %–0.25 % dexamethasone into a PDMS-based 3D scaffold to suppress the immune response, ultimately enhancing blood glucose levels and suppressing inflammatory pathways on M2 macrophages. Several recent studies utilized PDMS scaffolds as an oxygen vehicle for transplanted islets [331] , [332] . To mitigate the negative effects induced by hypoxic conditions post-transplantation at the extra-hepatic site, Liang et al [333] incorporated calcium peroxide in the PDMS scaffold.…”