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University Hospitals in Geneva are finalizing the latest evidence to initiate cell transplants of porcine origin in humans to treat diabetes and liver disease.

Geneva has been prepared for years for the transplantation of cells of porcine origin into humans for the treatment of diabetes and liver failure. The University Hospitals of Geneva (HUG) together with Professors Leo Bühler and Philippe Morel are prepared to start xenotransplantation, from animal donors. Both surgeons are awaiting the latest authorizations to raise pigs in a suitable structure in Switzerland. For twenty years, the duo, Bühler-Morel have worked on diabetes, a disease that occurs when the pancreas does not secrete enough insulin to control blood sugar levels. It’s purpose is to help patients who do not respond to the usual treatment of insulin injection, between 6,000 and 8,000 people in Switzerland. “In these patients, the instability of the disease damages all organs. This causes the progressive deterioration of blood vessels, which can cause kidney failure, cardiovascular or brain damage. It can even lead to the amputation of a leg”, says Philippe Morel, head of the department of vascular surgery at the HUG. In order not to reach these cases, transplantation of the pancreas is sometimes considered. HUG practices a dozen annual transplants, but they are limited by the number of donors and the high risks and complications of this type of transplant.

Islets of Langerhans (Human pancreatic islets)

Another possibility is the transplantation of Islets of Langerhans, groups of cells housed in the pancreas that secrete insulin. Tested in the USA in the 1980s, the technique did not achieve the expected results. According to Leo Bühler “One in five patients stopped being insulin dependent after transplantation, but only temporarily”. In 1992, the HUGs developed one of only ten laboratories in the world capable of performing these pancreatic islet transplants in diabetic patients. “More than 200 people have been transplanted by this center, which is one of the largest in the world,” says Philippe Morel. Since then, new drugs have emerged, limiting rejection of pancreatic islets. “Now 80% of patients are no longer insulin dependent after transplantation,” says Leo Bühler. But sometimes two or three injections from the donor are necessary to accomplish this. And between three and five years later, only 25% to 30% of transplants remain insulin-independent. Fortunately, the pancreas still secretes some insulin, which helps prevent acute hypoglycemia.

The virtues of the pig

Taking into account these insufficient results and the great difference between the number of human donors (one hundred per year) and the number of potential beneficiaries (thousands), a third way has been developed: the transplantation of porcine pancreatic islets. Why the pig? For several reasons: first, because porcine insulin, very similar to human insulin, has been used since 1921 to treat diabetes with excellent results.

Later, because pigs represent an almost inexhaustible source. Massachusetts General Hospital in Boston, has offered Geneva six pairs of pigs conceived without viruses or bacteria – which for now are waiting in Brussels. Leo Bühler trained for five years in xenotransplantation in this same American hospital. For years the HUGs collaborated with a team from the École Polytechnique Fédérale de Lausanne (EPFL) to encapsulate porcine pancreatic islets. They need to be protected from massive rejection by the recipient. “The islands are encapsulated in a chemical material of biocompatible polymers, which prevent cellular contacts between the inside and the outside but allow insulin, oxygen, nutrients and glucose to pass through”, says Leo Bühler.

Is this ideal? Not quite, because the body still reacts against these polymers. “Scars form around them. Cells die asphyxiated over time. The cooperation with the EPFL has allowed testing of even more biocompatible polymers that give excellent results in small animals”. This is encouraging, according to Leo Bühler.

For Philippe Morel, the Geneva team accumulates several assets:

An experience in the grafting of pancreatic islets in diabetics, an expertise in xenotransplantation, the ability to encapsulate porcine cells and access to pigs without viruses or bacteria. “In addition, the Swiss Law on transplants authorizes this type of transplantation from pig donors”, says the professor. What do Jewish and Muslim people who practice these therapies think? “The question arose in the 1980s when surgeons began to implant biological heart valves of porcine origin” says Leo Bühler. The Islamic and Jewish religions see no problem with the implantation of tissues, cells or organs of porcine origin for medical purposes. The only limitation is the oral intake of pork.

Healing the Liver Porcine

Cells have another therapeutic virtue, curing acute liver failure. “Dozens of people die every year because they cannot be transplanted in time”, observes Leo Bühler. Thanks to the collaboration with France, we can obtain organs, but this is not enough. Using porcine liver cells could be a solution. Even if it only works for a few months, it is not serious: they guarantee the transition while the liver of the patient regenerates. “They would immediately resume their normal functioning by themselves.” To start the first clinical trials, the Geneva team has been working for two years with Swissmedic, the Swiss Agency for Therapeutic Products, to finalize the protocols necessary to apply them to humans.

The researchers want to expand the Arare farm , which is already used to raise research animals, so that in addition to French pigs it can host American pigs in sterile conditions. A clinical information meeting was held on February 24, 2016 in a hotel in Geneva, with the participation of the State Councilor responsible for Health, Mauro Poggia (TDG).

Reference of published article: Le porc, avenir de l’homme (The pig, the future of man) Médecine – La xénotransplantation Tribune de Genève Suisse par Sophie Davaris (Scientific information published in the Tribune newspaper in Geneva Switzerland on Nov 15 / 2015)