gms | German Medical Science

Introduction: In the early post-transplant period, transplanted islets are affected by inflammatory reactions and hypoxia. Additionally, immunosuppressors are associated with islet toxicity and significant morbidity in the patient. Thus, strategies to promote islet engraftment and immune-tolerance are the moving-spirit for the proposed study: Utilization of a specially engineered macrochamber that provides complete immuno-isolation of islet grafts and allows for controlled oxygen supply.

Materials and methods: Isolated rat islets were macro-encapsulated and transplanted subcutaneously into STZ-induced diabetic rats. Oxygen supply was provided by daily s.c.-refuelling during follow-up of 90 days. The model was carried out in a syngeneic and allogeneic setting.

The model was then translated to large animals using minipigs as recipients of allogeneic and xenogeneic encapsulated islets. To test for biocompatibility and graft survival, healthy pigs were implanted with islet-containing devices. After 4 weeks the devices were explanted and assessed for viability and function. In first pre-clinical experiments, the device was tested in pancreatectomized diabetic minipigs.

Results: All transplanted rats showed normalization of blood glucose independent of syn- or allogeneic setting. After retrieval, the animals quickly reverted to hyperglycaemia. Explanted islets were morphologically and functionally intact. In the large animal model, biocompatibility of the device could be proven by absence of local inflammation or fibrosis. Retrieved islets were found intact and functional. Diabetic minipigs showed immediate and sustained normoglycemia following device implantation.

Conclusion: We have demonstrated successful application of an oxygen-refuelling macrochamber for sustained islet function and immuno-protection in rodent and large animal diabetes-models. This work opens up avenues for porcine islet xenotransplantation.