For years, the University Hospitals of Geneva (HUG) has been preparing to conduct cell transplantation using porcine (pig) cells to treat diabetes and liver diseases. This advancement is the fruit of two decades of research, primarily led by two eminent surgeons at the HUG, Professors Dr. Leo Bühler and Dr. Philippe Morel. At present, they await final approvals to breed pigs in Switzerland for this purpose. This innovative approach aims to help patients with diabetes that is unresponsive to traditional insulin treatments, which affects thousands of people in Switzerland.
In diabetes, the pancreas fails to produce sufficient insulin to regulate blood sugar, which can cause serious health issues if not managed properly. “In these patients, the instability of the disease damages all organs,” Dr. Morel, head of the department of vascular surgery at the HUG, said. “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.” To avoid severe diabetes complications, pancreas transplantation is sometimes conducted. The HUG conducts about a dozen such transplants yearly, but the feasibility of this procedure is constrained by donor scarcity and a high risk of complications.
Islets of Langerhans (Human pancreatic islets)
Another option to treat diabetes is the transplant of Islets of Langerhans, a group of cells that secrete insulin in the pancreas. This technique was first explored in the 1980s in the USA but initially fell short of expectations. According to Dr. Bühler, “One in five patients stopped being insulin dependent after transplantation, but only temporarily.” However, in 1992, the HUG developed a laboratory center capable of performing successful pancreatic islet transplantations. “More than 200 people have been transplanted at this center, which is one of the largest in the world,” Dr. Morel stated. This success is partly due to advances in immunosuppressive drugs that prevent transplant rejection. While about 80% of patients no longer need insulin injections post-transplant, the rate of maintaining insulin independence drops to 50% of patients at five years later. Nevertheless, the transplanted cells continue to produce some insulin, preventing episodes of hypoglycemia and mitigating disease severity.
The virtues of the pig
The vast gap between the limited number of human donors (one hundred per year) and the high demand for cell transplants (thousands per year) necessitates an alternative solution. Therefore, scientists have attempted transplantation with porcine (pig) pancreatic islet cells instead of human donors’ cells. Pigs are chosen for several reasons, notably because porcine insulin is remarkably similar to human insulin and has been successfully used to treat diabetes since the 1920s.
Moreover, pigs offer a nearly inexhaustible supply of cells for transplantation. The Massachusetts General Hospital in Boston has provided the HUG with six pairs of germ-free pigs, currently housed in Brussels. Professor Dr. Bühler, with five years of xenotransplantation (xeno- means cross-species) training at this hospital, and the HUG collaborated with the École Polytechnique Fédérale de Lausanne (EPFL) team to encapsulate porcine pancreatic islets with biocompatible polymers to prevent them from being rejected by the recipient’s immune system. The biocompatible polymers, Dr. Bühler explained, allow essential molecules like insulin, oxygen, and nutrients to pass through while preventing direct cellular contact.
However, this technique is not perfect as the body may still react to the polymers, forming scar tissue and leading to cell asphyxiation (oxygen-deprived) over time. That said, collaboration with the EPFL has led to the development of more biocompatible polymers, Dr. Bühler noted, which have shown encouraging results in small animal tests, representing a significant step forward.
Overall, Dr. Morel underscores the extensive expertise and resources of the HUG team, particularly in pancreatic islet grafting, xenotransplantation, encapsulating porcine cells, and access to pathogen-free pigs. “In addition, the Swiss law on transplants authorizes this type of transplantation from pig donors,” Dr. Morel said. What about the religious perspectives of Jews and Muslims? Such discussion arose in the 1980s when surgeons implanted porcine heart valves. The Jewish and Islamic religions only forbid the oral intake of pork but did not oppose xenotransplantation from pigs for essential medical purposes.
Healing the Liver Porcine
Porcine cells also offer a potential treatment for acute liver failure, a condition that claims thousands of lives every year due to the lack of timely transplants. Even if the xenotransplantation of porcine liver cells only works temporarily, Dr. Bühler noted that this procedure could buy time until the patient's liver can regenerate. The liver is a special organ that has the capacity to regenerate even if only 10% of it remains. For over two years, the HUG team has been coordinating with Swissmedic, the Swiss Agency for Therapeutic Products, to launch the first clinical trials to explore the therapeutic potential of xenotransplantation of porcine liver cells.
Plans are underway to expand the Arare farm, which is already being used to breed research animals, to further accommodate American pigs in addition to French pigs under sterile conditions. The health state councilor, Mauro Poggia, attended a meeting regarding this expansion on February 24, 2016, in Geneva, highlighting the project's importance and collaborative efforts.
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)