Xenotransplantation as a therapy for type 1 diabetes: Pig beta cells show great promise in an animal model

April 23, 2012

Transplantation of a whole pancreas or isolated insulin-producing beta cells are the only therapy to cure type I diabetes. However, the shortage of organ donors limits this approach to only few patients. LMU researchers have now shown that beta cells from genetically modified pigs can effectively restore pancreas function and can protect porcine beta cells from immune rejection in animal models.

Type 1 diabetes is caused by autoimmune destruction of the insulin-producing beta cells. Over 250,000 patients suffer from type 1 diabetes in Germany who are treated with daily insulin injections to maintain . Replacement of the destroyed beta cells by transplantation of either a complete pancreas organ or isolated human beta cells is the only effective way to cure the disease. However, due to the shortage of this method can be offered to only few patients. As an alternative approach researchers are exploring xenotransplantation, i.e. transplantation of the organ from another species. The most obvious barrier in xenotransplantation is the strong against the transplant. A research team led by LMU's Professor Eckhard Wolf and Professor Jochen Seissler has now generated a genetically modified strain of pigs whose beta-cells restores and inhibit human-anti-pig immune reaction. So far, the efficacy of this approach has been demonstrated only in an experimental mouse model. "Whether the strategy will work in humans remains to be demonstrated," says Professor Wolf. "Nevertheless, we consider the approach as very promising and plan to test it further in other settings."

is caused by an autoimmune reaction which ultimately leads to the destruction of the insulin-producing cells in the pancreas, and usually becomes manifest during adolescence. Thereafter, insulin must be administered by regular . Since cannot reproduce the complex pattern of physiologically controlled , patients are at risk of hypoglycemia and many patients develop severe vascular complications such as myocardial infarction or stroke.

Transplantation of a healthy pancreas or pancreatic beta cells that synthesize insulin may represent the best treatment option. Unfortunately, the availability of donor organs falls far short of requirements. Over the course of the last several years, fewer than 200 pancreas transplantations have been carried out. "Pigs represent a possible alternative source, because glucose metabolism in this species is very similar to that in human beings," Professor Seissler points out.

Pig insulin differs from its counterpart in humans at only a single amino acid, and has been used successfully in the treatment of diabetic patients for decades. However, pig cells inevitably provoke an immune reaction leading to the destruction of the transplanted tissue. One way of avoiding this difficulty is to encapsulate the foreign tissue in a biologically inert material that is permeable to insulin but not to cells of the immune system. However, the drawback of this approach is the restricted supply of oxygen and essential nutrients to the transplanted cells, thereby reducing its lifespan.

Wolf and his team chose a different route. For the first time they generated genetically modified pigs that express the protein LEA29Y specifically in beta cells. LEA29Y effectively inhibits the activation of a class of immune cells that are required to initiate a rejection reaction. The researchers then transplanted these cells into a diabetic mouse strain that has a humanized immune system. Seissler's group showed that these mice were able to restore glucose metabolism and were protected form human-anti-pig rejection. As Wolf is quick to point out, "It is not yet clear whether this will also work in humans. However, we will now attempt to validate the effects of this very promising approach using expressing immune modulators in other transplantation models." (suwe)

Explore further: Connexins: Providing protection to cells destroyed in Type 1 diabetes

More information: Paper: Diabetes online, 20. April 2012 diabetes.diabetesjournals.org/ … abstract/db11-1325v1

Related Stories

Connexins: Providing protection to cells destroyed in Type 1 diabetes

November 7, 2011
Type 1 diabetes is a lifelong disease characterized by high levels of sugar (glucose) in the blood. It is caused by the patient's immune system attacking and destroying the cells in their pancreas that produce the hormone ...

Pig to primate transplants show promise for diabetes

November 9, 2011
(Medical Xpress) -- Scientists exploring a potential cure for diabetes have shown that transplanting insulin-producing cells from embryonic pigs into diabetic monkeys can dramatically lower blood sugar levels, though not ...

Scientists use uterine stem cells to treat diabetes

September 14, 2011
Controlling diabetes may someday involve mining stem cells from the lining of the uterus, Yale School of Medicine researchers report in a new study published in the journal Molecular Therapy. The team treated diabetes in ...

Chemical produced in pancreas prevented and reversed diabetes in mice

June 28, 2011
A chemical produced by the same cells that make insulin in the pancreas prevented and even reversed Type 1 diabetes in mice, researchers at St. Michael's Hospital have found.

Recommended for you

Diabetes pill might replace injection to control blood sugar

October 17, 2017
(HealthDay)— An injectable class of diabetes medication—called glucagon-like peptide-1 or GLP-1—might one day be available in pill form, research suggests.

Skimping on sleep may contribute to gestational diabetes

October 17, 2017
The amount of time spent sleeping in the United States has dropped significantly in the past twenty years with almost a quarter of women and 16 percent of men experiencing insufficient sleep. Now, a new study has found that ...

Artificial pancreas performs well in clinical trial

October 16, 2017
During more than 60,000 hours of combined use of a novel artificial pancreas system, participants in a 12-week, multi-site clinical trial showed significant improvements in two key measures of well-being in people living ...

Omega-6 fats may help prevent type 2 diabetes

October 11, 2017
The risk of developing type 2 diabetes could be significantly reduced by eating a diet rich in omega-6 polyunsaturated fats, a new study suggests.

Where there's type 1 diabetes, celiac disease may follow

October 10, 2017
(HealthDay)—Parents of young children with type 1 diabetes need to be on the lookout for symptoms of another autoimmune condition—celiac disease, new research suggests.

Type 1 diabetes and the microbiota—MAIT cells as biomarkers and new therapeutic targets

October 10, 2017
Together with colleagues from AP-HP Necker–Enfants Malades Hospital in Paris, scientists from the Cochin Institute (CNRS / INSERM / Paris Descartes University) have discovered that the onset of type 1 diabetes is preceded ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

winthrom
not rated yet May 16, 2012
Considering the human supply is small and the need is large, Xenotransplantation as a therapy for type 1 diabetes approach sounds ideal. This may also apply to heart, liver, lung, and other transplants in the future.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.