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

Project description

A new platform assessing diabetes treatment

Finding an effective diabetes treatment is not easy. The challenge lies in the inability to assess beta-cell function and survival non-invasively and at single-cell resolution in living organisms. Traditional methods lack the necessary precision, and invasiveness often compromises results. In this context, the ERC-funded SILORGS project will address this issue by transplanting genetically engineered sensor islet organoids into the eyes of mice. Specifically, researchers enable microscopic imaging through the cornea, offering a natural window into beta-cell activity. These organoids, responsive to diabetic conditions, allow longitudinal monitoring of glucose responsiveness, Ca2+ handling, beta-cell mass, and proliferation. The project aims to establish a robust in vivo imaging platform for early validation of potential diabetes treatments.

Objective

To develop new drugs for 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. 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 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. 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, and 4) proliferation. 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. 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.

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Host institution

KAROLINSKA INSTITUTET
Net EU contribution
€ 150 000,00
Address
Nobels Vag 5
17177 Stockholm
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Beneficiaries (1)