Tissue-engineering and intraocular transplantation of optimally functioning insulin-secreting islet organoids

Pancreatic islet transplantation is essential for treating insulin-dependent diabetes.

Outcome varies due to transplantation site, quality of islets and the fact that transplanted islets are affected by the same challenges as in situ islets.

We combine tailor-making islet organoids by tissue engineering with using the anterior chamber of the eye (ACE) as a transplantation site that allows monitoring and local modulation of islet cells.

Genetic engineering of islet organoids allows generating 1) standardized material optimized for transplantation, function and survival as well as 2) organoids suitable for monitoring (sensor islet organoids) and treating (metabolic islet organoids) insulin-dependent diabetes.

Our overall aim is to create a platform allowing monitoring and treatment of insulin-dependent diabetes in mice that can be transferred to large animals for validation.

The objective is to combine tissue engineering of islet organoids, transplantation to the ACE (years 1-4), synthetic biology, local pharmacological treatment strategies (years 3-5) and the development of novel micro-electronical/micro-optical readout systems for islet cells (years 1-5).

This regenerative medicine approach will 1) lay the foundation for high-precision medicine in diabetes, 2) identify novel druggable targets and biomarkers for disease progression and treatment evaluation and 3) establish an in vivo screening platform for efficacy validation of novel lead-compounds for treatment of diabetes.