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About the Project

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.

Islets 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 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.

Our strategy

The VANGUARD project aims to generate a vascularized  and  immune-protected  bioartificial  pancreas that  can  be  transplanted  into  non-immunosuppressed patients; it combines 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 will be 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 pro-tection and anti-inflammatory properties.
  • Islet cells: regulated insulin secretion.
  • Blood outgrowth endothelial cells (BOECs): angiogenesis for construct revascularization.

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

The VANGUARD workplan

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 874700

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