Sensor islet organoids (SILORGS) for in vivo identification of anti-diabetic drugs

Introduction

To develop new drugs for the treatment of diabetes, there is an immediate need for an in vivo approach allowing the assessment of β-cell function and survival in the living organism non-invasively, longitudinally, and at single-cell resolution.

Methodology

We therefore transplant genetically engineered sensor islet organoids into the anterior chamber of the eye of mice for functional microscopic imaging. Using the cornea as a natural body-window, following their engraftment, various aspects of β-cell function and survival can be readily imaged in these organoids.

Functional Studies

Functional studies demonstrate that engrafted islet organoids in the eye respond to the diabetic milieu of diabetic mouse models. We have extensively in vitro tested fluorescent biosensors that reflect key events in β-cell function and survival.

In Vivo Monitoring

Following intraocular transplantation of mouse and human islet organoids expressing biosensors in their β-cells into healthy or diabetic mice, they will allow non-invasive, longitudinal in vivo monitoring of:

1. Glucose responsiveness
2. Ca2+ handling
3. Functional β-cell mass
4. Proliferation

Objective

Based on the in vitro tested biosensors, the major objective is to establish a robust pharma-industry in vivo imaging platform for validating newly developed diabetes treatment lead compounds in early drug development. This screening service shall be performed on a commercial basis.

Milestone

The milestone of this proposal, to be achieved within 18 months, is the validation of the sensor islet organoid-based in vivo platform for testing the effects of new potential diabetes medicines on human β-cell function and survival in normal and diabetic mice.