Beta cell replacement therapies aim to provide insulin on demand from cells implanted in the body, but, today, the shortage of donor beta cells and the need for chronic immunosuppression limit its widespread clinical adoption.

Breakthrough T1D is funding researchers around the world working on every aspect of cell replacement technologies to make them a reality—a cure—for type 1 diabetes (T1D). There’s a lot to figure out an many obstacles to overcome until these therapies realize their potential. These include:

  • Cell Supply: How do we make enough cells for everyone who needs them? Do we use a renewable beta cell source from stem cells or animal models?
  • Immunoprotection: How do we protect the cells from the hostile environment in the body once they are transplanted—and where is the best place for them to be transplanted?
  • Oxygen and Other Nutrients: How do the transplanted cells get the resources they need to survive while keeping the immune system out?

Several approaches, however, are aiming to make these obstacles a thing of the past. Read more below.

Blood Vessel Growth + Local Immunosuppression = A Win for Islet Cell Therapy

A way to combine islets—the group of pancreatic cells that produce insulin and glucagon—with blood vessels before transplantation would give them a virtually infinite supply of oxygen and nutrients, but it exposes the islets to the immune system, requiring systemic immunosuppression to prevent rejection. A novel encapsulation approach that integrates blood vessel growth for islets with effective immune evasion to prevent rejection could work.

Encapsulation: An advanced form of transplantation where a material is designed to keep cells protected from immune attack, while letting insulin out and letting oxygen and other nutrients in.

Enter the NICHE. It stands for Neovascularized Implantable Cell Homing and Encapsulation device. It is a quarter-sized device with two reservoirs—one for islets which have undergone the process of developing blood vessels and one for local immunosuppressant delivery—for the transplantation of islets to treat T1D. It is the first platform that integrates both blood vessel growth plus local immunosuppression into a single, implantable device.

In animal models, this device restored healthy glucose levels and eliminated T1D symptoms for more than 150 days while avoiding the adverse effects of anti-rejection therapy by administering immunosuppressive drugs only where the transplanted islet cells were located.

The results pave a path for the continued translational development of the NICHE technology, which has the potential to transform the field of islet transplantation.

Engineering a Pancreas-Like Organ for Transplantation

An unlimited source of less immunogenic islets? Check. Blood vessel growth prior to transplantation? Check. A novel scaffold to put these into? Check.

What does this mean?

You have an immune-protected, functional pancreatic organ—the first bioengineered device aimed to treat T1D.

What’s more? Results showed immediate function upon transplantation, preserving normal blood-sugar levels for up to 18 weeks.

Eventually, with further testing, this could be the next phase of cell replacement therapy, overcoming the current limitations in islet transplantation to generate a bioengineered device for the treatment of T1D.

Transplantation Without the Need for Any Immunosuppression

Vertex Pharmaceuticals—which acquired Semma Therapeutics in 2019 and ViaCyte in 2022, both of which had Breakthrough T1D or Breakthrough T1D T1D Fund support, with the goal of developing stem cell-derived replacement therapies for T1D—has a new first: No immunosuppression.

VX-264 takes the stem cell-derived therapy VX-880—which is being used to try to restore the body’s ability to produce insulin combined with immunosuppression—and encapsulates it with an immunoprotected device. The trial will begin to recruit later this year.

In Vertex’s phase I/II clinical trial, the first person to receive VX-880 is 100% insulin independent 270 days after receiving the therapy.

“Advancing research in cell replacement is a core pillar of Breakthrough T1D’s research strategy and we have been a significant supporter of these and other promising approaches,” said Jaime Giraldo, Ph.D., Associate Director of Research at Breakthrough T1D. “There is a revolution in cell therapy technologies and approaches, which will bring us one day to finding cures for type 1 diabetes.”