About the Project

Project overview

  • Consortium

    9 partners from 5 countries

  • Budget

    € 6.8 million

  • Duration

    01.01.2020 – 30.06.2025

Diabetes

Type 1 diabetes results from the autoimmune destruction of insulin-producing beta-cells. These cells are located in mini-organs, called islets of Langerhans, which are distributed within the pancreas. The disease usually starts in childhood or young adulthood. It  is  the  most  common chronic disease in children and adolescents. Type 1 diabetes can be cured by transplantation, either of the whole pancreas or of isolated islets. Europe is the region with the highest reported number of children and adolescents affected by Type 1 diabetes.

Islet transplantation

Pancreas transplantation is an efficient procedure for restoring blood sugar control.  However, this is a major surgical procedure, plagued by a high complication rate. It is only performed in a minority of patients with type 1 diabetes because of the marked imbalance between organ donors and individuals suffering from the disease.

Cell therapy for type 1 diabetes is currently performed in a small number of selected patients by transplantation of allogeneic islets of Langerhans, with good functional outcomes. Islet transplantation is a valuable first step toward offering a cure for all patients with type 1 diabetes but this therapeutic approach is hampered by several issues:

  • A poor engraftment due to inflammatory and hyposia phenomena at the time of transplantation, which leads to the need of multiple donors (multiple transplants) for a single recipient
  • An attrition rate of ≥50% at 5 years for full islet graft function (insulin-independence)
  • The imbalance between the number of patients with type 1 diabetes and the number of organ donors
  • The need for lifelong immunosuppression to avoid graft rejection.

What was our strategy

The VANGUARD project aimed to generate a vascularized and immune-protected bioartificial pancreas that can be transplanted into non-immunosuppressed patients; it combined advanced tissue engineering strategies, such as 3D organoid generation, hydrogel design,  bioartificial organ assembly and  CRISPR-Cas9  gene editing. The bioengineering of insulin-producing 3D organoids and their assembly into a bioartificial endocrine pancreas was based on these components:

  • Hydrogel: an extra-cellular matrix nearly identical to that of native islets, which provides mechanical protection,  anti-inflammatory properties, and anti-apoptotic properties, as well as modulates insulin secretion.
  • Gene-edited amniotic epithelial cells: immune protection and anti-inflammatory properties.
  • Islet cells: regulated insulin secretion.
  • Blood outgrowth endothelial cells (BOECs): angiogenesis for construct revascularisation.

Organoid manufacturing was performed using the Sphericalplate 5D, a patented cell culturing platform to be medically approved as a medical device class IIa.

The VANGUARD workplan, 2020-2025