The partners cooperating in the Drive project are determined to break new ground for islet transplants, i.e. transplants of insulin-producing clusters of pancreatic cells. They are developing a minimally invasive way to establish and maintain donated islets in recipients who would otherwise need frequent injections.
The grafts will be inserted in a fold of tissue in the abdomen, essentially creating an artificial organ composed of living cells. Drive is developing microcapsules that will house the implanted cells, a substance that will provide them with a suitable environment within these capsules, and a catheter that will enable doctors to insert the capsules using a keyhole procedure.
With reference to the islet cells that produce the insulin, the so-called beta cells, the partners have named this combination of innovations the “beta system”. It is intended for patients whose islets have been targeted and destroyed by the body’s immune system, which is the cause of type 1 diabetes. However, it could eventually also benefit persons suffering from type 2 diabetes, whose bodies don’t produce enough insulin or don’t use it properly.
Pockets of independence
Islet transplants can greatly improve the quality of life of diabetics who rely on insulin shots. Healthy islets don’t just produce the precious hormone; they adjust their output in line with the blood sugar levels they detect. A successful islet transplant thus reduces these patients’ burden considerably by freeing them of the obligation to work out how much insulin they need and to administer accordingly.
That said, the current technique has its limitations, says Drive coordinator Garry Duffy of the Royal College of Surgeons in Ireland. It involves injecting the donated islets into an abdominal vein. Many of them will fail to take, he explains, and the remainder will soon die off. Immunosuppressant drugs are needed throughout to keep the recipient’s body from rejecting the foreign cells.
The Drive project, launched in June 2015, is taking a fresh look at the possibilities. “We will give the islets something to hold on to and so increase their uptake in the body,” says Duffy. More specifically, the partners intend to insert the islets into small capsules, create a fold in the lining of the recipient’s abdomen and establish the capsules inside this “pocket”.
At the moment, constructing such a fold would require open surgery, says Duffy. Drive aims for a keyhole approach instead. “We want to develop a new surgical procedure to deliver these capsules in a minimally invasive way,” he notes.
Archipelagos of anchored islets
Individual capsules will contain several thousand islets suspended in a gel that replicates the pancreas, Duffy explains. This biomaterial should enable the islets to make themselves at home once they have connected to the blood supply through pores in the capsule’s shell.
To avoid rejection, the capsules will release an immunosuppressant locally. In contrast with the current method, there would thus be no need for patients to take anti-rejection drugs that affect their entire body. When the implanted islets begin to decline, the capsules can be retrieved, replenished and reinserted quite easily, says Duffy.
Of course, it is still early days — the project has only just begun, and while the aim is clear, the research needed to reach it still has to be carried out. By the end of the four-year funding period, the partners intend to complete the development of the beta system and demonstrate its potential.
Clinical trials and further development will then be needed to take it forward. This process could take another five years, says Duffy, adding that by this time it may also be possible to grow new islets inside a recipient’s abdomen using stem cells. Drive’s capsules, he notes, will be designed to work for these as well.