Creating stem cells from mini-pigs promises to improve treatments

A breed of pig called the Wisconsin Miniature Swine — created by a team of UW-Madison scientists — will help researchers better model and understand human disease. Photo: Jeff Miller

Minipig cells pave the way for better stem cell therapies.

A team led by the University of Wisconsin-Madison Center for Stem Cells and Regenerative Medicine searcher Wan-Ju Li offers an improved way to create a particularly valuable type of stem cell in pigs – a cell that could speed the path to treatments that restore damaged tissue for conditions ranging from osteoarthritis to heart disease in human patients.

In a study published in Scientific reports, Li’s team also provides insight into the reprogramming process that transforms cells in one part of the body into pluripotent stem cells, a basic cell type that can transform into any type of tissue. This new knowledge will help researchers investigate treatments for a wide range of diseases.

The researchers turned to pigs, a well-established animal model for potential human treatments, because translating the research to improve human health is hugely important to Li, a professor of Orthopedics and Rehabilitation and Biomedical genius. He has spent much of his career studying cartilage and bone regeneration to develop innovative therapies to help people.

Li and the members of his Musculoskeletal Biology and Regenerative Medicine Laboratory obtained skin cells from the ears of three different breeds of minipigs – the Wisconsin minipig, the Yucatan minipig, and the Göttingen minipigs.

Wan-Ju Li holds a sample of collagen fiber on a piece of aluminum foil.  Gwen and Karen Plunkett stand to the right and look at the sample.

Wan-Ju Li (left), a researcher at the University of Wisconsin-Madison Center for Regenerative Medicine and Stem Cells, shows a sample of collagen fibers to Gwen Plunkett and Karen Plunkett. Funding from the Plunkett Family Foundation helped research into cartilage repair therapies through the UW-Madison Musculoskeletal Research Program.

The researchers reprogrammed the cells to create induced pluripotent stem cells and demonstrated that they had the ability to become different types of tissue cells. Pluripotent stem cells are the master cells of the body and they are of inestimable value for medicine since they can be used for the regeneration or repair of damaged tissues.

The results of this study suggest that the miniature pig is a promising animal model for preclinical research. The team plans to use the established porcine model to replicate their recent findings on cartilage regeneration in rats, as reported in Scientists progress. Cartilage regeneration in animals, even more similar to humans, brings science closer to helping patients with joint diseases such as osteoarthritis.

“By successfully developing induced pluripotent stem cells from three different breeds of mini-pigs, we learned that we could take somatic cells from the skin of these pigs that we programmed ourselves, and then inject them back into the same animal to repair cartilage defects,” Li explains. “Or we can create induced pluripotent stem cells from the skin cell that carried the gene causing cartilage diseases such as chondrodysplasia and put them in the box of culture and use them as a disease model to study disease formation.”

Li says the approach can be applied to regenerative therapies targeting any organ or tissue.

The team also discovered that a particular protein complex involved in the management of gene expression, and linked to cell growth and survival, could influence the efficiency with which induced pluripotent stem cells are generated. “Although we were able to create induced pluripotent stem cells from the three different strains of pigs, we noticed that some pigs had higher reprogramming efficiency,” says Li. “So the second part of our findings, important in biology is to understand how these differences occur and why.”

These findings, he says, can translate directly to understanding differences in the efficiency of induced pluripotent stem cell generation between individuals – a study showed cell reprogramming efficacy varying by age and ancestry – and leading to better tailored therapies.

“I want to make sure that our findings in stem cell research can be used to help people,” Li says. carries significant weight in terms of potential for translational stem cell research and the development of therapeutic treatments.”

Interest in advancing these treatments has grown, and while the study was funded in part by the National Institutes of Health, Li also received support from the Milwaukee-based Plunkett Family Foundation through their donation to the UW Stem Cell & Regenerative Medicine Center. After hearing about Li’s research, Gwen Plunkett and her daughter Karen visited Li’s lab in 2019 to learn more. They were inspired to support stem cell research for cartilage regeneration.

“Innovation in medicine triggers critical changes, for the world and the survival of our species, and the mission of the Plunkett family is to be a catalyst in stem cell research and regenerative medicine,” says Karen Plunkett .

The donation had a profound impact, Li says, allowing him to pursue his goal of using stem cells to help patients with osteoarthritis and other joint diseases – many of whom write to his lab regularly in the hope find a clinical trial opportunity.

“I have to keep saying, ‘Wait another two or three years, maybe we’ll be ready for a clinical trial,'” Li said. larger animal studies to deliver on our promise. At least this way I can bridge the gap between the lab and clinical trials, because larger animals need to be studied before embarking on a clinical trial.

This research was supported by grants from the National Institutes of Health (R01 AR064803), the Plunkett Family Foundation and the UW Carbon Cancer Center.

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