At U, gene editing boosts hopes for pig cell transplants to treat diabetes

New gene-editing research at the University of Minnesota is boosting hopes of using cells from pigs to treat or even reverse Type 1 diabetes.

While the U has been a national leader in the study of animal-to-human transplants, known as xenotransplants, it has struggled to overcome the body's natural inclination to reject foreign cells.

Even human-to-human transplants require recipients to take potent drugs for life to prevent their bodies from rejecting donated organs or cells.

Prospects improved this year, though, with the availability of CRISPR — a new, fast and cheap method of editing genes — and the recruitment of researchers to work with it.

"In less than a year's time, we've just made a tremendous amount of progress," said Christopher Burlak, who the U recruited this spring because of his expertise with CRISPR and genetic modifications in pigs.

The ultimate goal, he said, is creating "stealth" islet cells from a pig's pancreas that are so familiar to the human body that they can be transplanted without the need for anti-rejection medications.

That paired with the ability to mass produce islet cells from a pig's pancreas would be a turning point, said Dr. Bernhard Hering, director of the U's islet cell transplant program. "If you put those two things together, it would get very close to what people would refer to as a bona fide cure of diabetes."

Most use regular insulin injections to manage the disease, but the U has been the leading institution nationally in human pancreas and ­experimental islet cell transplants to treat and in some cases reverse the disease.

Pigs are the leading provider of islet cells, but evolution has resulted in the deletion of some genes in humans that remain functional in pigs — making it easy for the human immune system to reject pig cells if they are transplanted.

While the ability to edit genetic sequences has existed for years, the discovery of CRISPR in the last two years has accelerated genetic research. It is based on the discovery of an enzyme known as Cas9 that can be directed in a way that disrupts DNA and allows for the insertion of desired genetic sequences.

Genetic modifications that once took years now take months, Burlak said.

Using CRISPR methods to delete genes from pig DNA might prevent pig islet cells from being attacked, Burlak said. "If we can delete a few genes to make them look a little more human … then we can blunt the immune response."

How aggressively to use islet cell transplants, which remain experimental, has been a lingering scientific question because insulin injections can manage diabetes for most people while transplants require immunosuppressive drugs that leave people at risk for infections, cancers and other complications.

Donor islet cells from humans also are in short supply, which is why Hering pursued xenotransplantation and the potentially limitless supply of pig cells.

That promise seemed tantalizingly close in 2006, when Hering's research proved that transplants of pig islet cells could reverse diabetes in ­monkeys.

The Spring Point Project, founded by a Duluth businessman with a diabetic son, then raised millions to build a high-security facility in New Richmond, Wis., where ultraclean pigs could be raised for transplant and research purposes.

But the immune system problem and other barriers stymied predictions of human trials taking place by now.

Burlak shares the motivation of Spring Point's founder, Tom Cartier, in that he also has a son with Type 1 diabetes. Burlak switched his medical career to diabetes research after his son's diagnosis ­several years ago.

He couldn't discuss findings from his ongoing research, which must be vetted and published in professional scientific journals first. But early tests of CRISPR-produced pig islets have shown promise in making them tolerable.

"What we want to engineer are stealth islets that go unrecognized by the human immune system," he said. "If that were the case, you can imagine a scenario where you won't need immune suppression, because you won't have anything to suppress against."