Abstract

Regenerative medicine using human or porcine β‐cells or islets has an excellent potential to become a clinically relevant method for the treatment of type‐1 diabetes. High‐resolution imaging of the function and faith of transplanted porcine pancreatic islets and human stem cell–derived beta cells in large animals and patients for testing advanced therapy medicinal products (ATMPs) is a currently unmet need for pre‐clinical/clinical trials. The iNanoBIT EU H2020 project is developing novel highly sensitive nanotechnology‐based imaging approaches allowing for monitoring of survival, engraftment, proliferation, function and whole‐body distribution of the cellular transplants in a porcine diabetes model with excellent translational potential to humans. We develop and validate the application of single‐photon emission computed tomography (SPECT) and optoacoustic imaging technologies in a transgenic insulin‐deficient pig model to observe transplanted porcine xeno‐islets and in vitro differentiated human beta cells. We are progressing in generating new transgenic reporter pigs and human‐induced pluripotent cell (iPSC) lines for optoacoustic imaging and testing them in transplantable bioartificial islet devices. Novel multifunctional nanoparticles have been generated and are being tested for nuclear imaging of islets and beta cells using a new, high‐resolution SPECT imaging device. Overall, the combined multidisciplinary expertise of the project partners allows progress towards creating much needed technological toolboxes for the xenotransplantation and ATMP field, and thus reinforces the European healthcare supply chain for regenerative medicinal products.

Highlights

  • Diabetes is one of the most challenging and economically important areas in medicine

  • About 10% of these subjects suffer from type-1 diabetes (T1D), which involves immune-mediated destruction of the insulin-producing pancreatic beta cells and requires exogenous insulin replacement

  • For patients with recurrent life-threatening hypoglycaemia, pancreas or islet transplantation is considered as ultimate therapeutic option,[2] which are able to normalize glucose homeostasis and prevent macro- and microvascular complications of diabetes

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Summary

Introduction

Diabetes is one of the most challenging and economically important areas in medicine. Immune isolation of cells by encapsulation with a permselective membrane, which protects cells against the recipient's immune system, but allows nutrient and oxygen supply,[9,10] is a promising strategy for allo- and xenogenic cell transplantation. This avoids lifelong immunosuppression and should be readily implemented in the clinic

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