University Medical Center of Groningen (UMCG)

PIs UMCG: Paul de Vos, Christina Krikke

About the UMCG

The laboratory of transplantation biology and immunoendocrinology of the University Medical Center of Groningen has a strong focus on the development of a bioartificial pancreas for the treatment of Diabetes type I. The group has published more than 100 papers on the subject and has established collaborative efforts with major companies and research groups in the area.

Relationship with DCTI

In the DCTI project research groups of different disciplines work together in order to develop a bioartificial pancreas which consists of a scaffold material with insulin producing cells. The scaffolds will be developed at the UT and the UMCG will concentrate on the biocompatibility of these scaffolds and on the efficacy of function of islets engrafted in prototype devices. The biocompatibility will be studied in different transplantation sites to study site specific responses. Extensive immunocytochemical analysis will be performed in the presence and absence of islets to gain mechanistic insight in the factors determining success and failure of the devices.  In cell seeding scaffolds the biocompatibility is not only determined by the host-responses but also by the compatibility of the seeded cells with their microenvironment. Adherent cell types such as islet-cells require many different adhesions to other cell types and the biomaterials to function properly. By performing high throughput analysis, adequate combinations of polymers will be selected to guarantee optimal functionality of the islets after implantation. The functionality will be tested by static incubation followed by perfusion experiments to follow the minute-to-minute regulation upon glucose challenge.  

The biocompatibility data will serve to design second generation scaffolds that fulfill the requirements that the scaffolds have to meet in order to allow optimal functional survival of islets. Next we will assess the efficacy of the devices as engraftment enforcing scaffold by comparing success rates and quality of glycemic control after implanting graded loads of islets syngenically into diabetic recipients into different sites. These data will serve to predict the islet-loads required for human islets and for the design of preclinical testings of human islets in the devices. Adaptations to the design will be applied when inadequacies are found. Finally autoimmune models will be applied for studying efficacy of function of allogenic mice allografts and human xenografts in the presence of clinical relevant immunosuppressive protocols. These data will serve as a technology platform to design and test the efficacy of novel scaffolds as carrier system for pancreatic islets applicable for human islet allograft transplantation in type I diabetic patients.