Abstract

Using Organoids to Re-Enact the Destruction of Human Beta cCells and Probe Novel Ways to Protect Them

Matthias von Herrath, Vice President and Senior Medical Officer, NovoNordisk; Professor La Jolla Institute, NovoNordisk

Replacement of beta cell function through stem cell derived islets has advanced tremendously in the recent years with the prospect of providing a potential cure for many patients.  However, newly implanted islets are unfortunately still subject to allo-immunity and recurring autoimmunity. To protect the cells and to circumvent the need for full immune suppression, which can have many adverse effects, various strategies are being used to stealthen the new islets. As there are many possibilities and human trials are lengthy and complex, we built an organoid-based 3D model to re-enact the events that lead to allo- and auto-immune destruction of beta cells together with the company In Sphero. This model allows for functional and quantitative readout of beta cell function on a rather continuous basis and thus can be an eminent tool to prioritize critical steps for a clinical translational strategy and define, which changes are needed to make stem cell derived islets immune evasive.