Stem cells are the brightest lights in osteoarthritis (OA) research. Because they have unique regenerative abilities and can differentiate into different types of tissue, they have the potential to repair worn-out cartilage — even generate new joints. Stem cells also provide an ideal platform for studying the genetics of OA, possibly leading to new patient-specific drugs.  

Researchers at Duke University in Durham, N.C., have spent years exploring how stem cells might benefit people with OA. A decade ago, Farshid Guilak, PhD, professor of orthopaedic surgery and an Arthritis Foundation-funded researcher, was the first to grow cartilage from fat-derived stem cells. Now, he and his team have engineered mouse cartilage using induced pluripotent stem cells, or iPSCs. Their research was recently published online in Proceedings of the National Academy of Sciences.

Cells With Benefits
iPSCs are differentiated adult stem cells reprogrammed to have the properties of stem cells isolated from embryos. They are created by injecting adult cells with four gene-regulating proteins – a technique that earned Shinya Yamanaka of Kyoto University the 2012 Nobel Prize in medicine.

Like embryonic stem cells, iPSCs can transform into a vast array of cell types and tissues, but without the ethical concerns associated with embryonic research. The cells in Dr. Guilak's study were derived from adult mouse fibroblasts. As important, iPSCs culture far more easily and abundantly than adult stem cells do.

"One of the limitations of [adult] stem cells is that after they have divided many times, they stop being stem cells, so it's difficult to make enough for repairing cartilage or screening for arthritis drugs," Dr. Guilak says. "What this study shows in a mouse model is that you can grow an unlimited supply of stem cells that can form cartilage."

But the proliferative nature of pluripotent cells has a downside. If iPSCs take a wrong turn on the way to becoming cartilage cells, they can form unusual tumors called teratomas. To prevent this, Brian Diekman, PhD, a postdoctoral researcher in the Guilak lab, tested different growth factors until he found some that encouraged cartilage production. Adding them to the culture medium nudged iPSCs in the right developmental direction. The iPSCs were also tailored to glow with a green fluorescent protein when they successfully transformed into cartilage cells to distinguish them from cells that didn't form cartilage.

Ultimately, about 10 percent of the iPSCs were usable. They were treated with more growth factors, and in three weeks, Dr. Guilak says, "they formed beautiful, cartilaginous pellets, rich in proteoglycans and collagen, which indicates they would work well repairing cartilage damage in the body." The iPSC cartilage was of higher quality than cartilage derived from adult bone marrow or fat tissue.

The next step will be to use human iPSCs from skin or fat tissue to test the cartilage-growing technique. If all goes well, human safety trials could start in five or six years.