Pig stem cells discovered by two animal science researchers at the University of Georgia reveal a better way to determine the safety of future stem cell therapies than rodent-based models.

Rodent studies are likely inadequate for testing many human therapies including pharmaceuticals, since 50 percent of all chemicals test positive as carcinogens, regardless of their source or identity, according to Thomas Hartung a professor in the Bloomsburg College of Public Health at Johns Hopkins University. He suggests that these rodent studies may be no better than a coin toss. As an example, some components in coffee appear to be carcinogenic in rodents, but in humans moderate coffee consumption may reduce the risk of cancer.

In 2010, UGA’s Steve Stice and Franklin West introduced to the world 13 pigs that show promise to unlocking the path to new therapies. The pigs today produced another positive finding: These adult-cell-sourced stem cells don’t form tumors in pigs.

“Pluripotent stem cells have significant potential for stem cell therapies,” said West, an animal science researcher in the UGA College of Agricultural and Environmental Sciences. “However, tests in mice often resulted in tumor formation that frequently led to death.”

Tackling tumors

This has raised concerns about the safety of induced pluripotent stem cells, or iPSCs, and cells derived from these stem cells. Until now, all iPSC safety studies have been performed only in rodent models.

“To address the concern, our research team studied tumor formation in pigs generated from pig iPSCs. Brain, skin, liver, pancreas, stomach, intestine, lung, heart, kidney, muscle, spleen and gonad tissues from all 11 pigs tested showed no evidence of tumors,” West said.

The absence of tumor formation in these pigs suggests that iPSCs can safely incorporate into tissues without tumor formation, despite previous results seen in the mouse.

“Being able to safely use iPSCs without the potential of causing tumors is essential for this promising stem cell therapy to become a viable treatment option,” said Stice, a Georgia Research Alliance Eminent Scholar in the College of Agricultural and Environmental Sciences.

“We now have graduate students working on making neural cells from the human and pig stem cells to help further the studies,” he said. “The human stem cells were effective in a rodent model for stroke, but rodent studies are not rigorous enough to start human clinical trials.”

“Over 700 drug treatments have gone to human clinical trials for stroke alone based on findings in rodents and have turned out not to be viable in humans. The pigs are much more human like, and they are going to be a much better model to study strokes” said West, who is heading up a cooperative project between the UGA Regenerative Bioscience Center and stroke researchers at Georgia Health Sciences University.

“This project will improve the speed and efficiency of treatment development for stroke and many other conditions and potentially reduce the number of nonhuman primates used in research,” West said.

Breeding success

In addition, the group has now bred these pigs produced from iPSCs and proved the stem cells did pass to the offspring. This also opens the door for producing better animal-sourced tissue for human regenerative medicine such as islet cells that produce insulin for diabetic patients.

To further their progress, the UGA Regenerative Bioscience Center, using iPSC technology, is working with researchers at Emory University to make pigs whose cells from the pancreas would demonstrate decreased rejection in human treatments.

“The next step would be to put these pig insulin-producing cells into other animals, potentially dogs or cats suffering from diabetes to see if it will produce insulin for them without being rejected,” Stice said. “So, it’s moving forward. Never as fast as we like, but it’s moving.”

Results of these studies were published in the October issue of Stem Cells.