Joint cartilage regrown in arthritic mice by a stem cell tweak

Like most machines, the human body tends to wear out faster at the points of articulation, where decades of stress are focused. Now, researchers at Stanford have found a way to induce cartilage tissue to regenerate in joints by tweaking the stem cells there.

Articular cartilage is the soft, shock-absorbing tissue that lies between bones in joints like knees and fingers. As it wears away with age or is damaged by injury, ongoing pain and inflammation can follow, leading to arthritis and other conditions.

“Cartilage has practically zero regenerative potential in adulthood, so once it’s injured or gone, what we can do for patients has been very limited,” says Charles K.F. Chan, co-senior author of the study. “It’s extremely gratifying to find a way to help the body regrow this important tissue.”

For the new study, the team investigated what’s going on after treatment by a technique called microfracture. This process involves drilling tiny holes into the surface of a joint, and it’s seen to stimulate the growth of new cartilage-like tissue. While it helps a little, the emphasis there is on “cartilage-like.”

“Microfracture results in what is called fibrocartilage, which is really more like scar tissue than natural cartilage,” says Chan. “It covers the bone and is better than nothing, but it doesn’t have the bounce and elasticity of natural cartilage, and it tends to degrade relatively quickly.”

Microfracture works by stimulating the skeletal stem cells in the joint to grow new tissue – it was just not quite the type of tissue we want. So in studies on mice, the team tested whether they could be made to grow cartilage instead. After all, as bone develops it goes through a phase of being cartilage – is it possible to pause it there?

To find out, the team used a molecule called bone morphogenetic protein 2 (BMP2) to kick off new bone formation after a microfracture procedure. But before it could become bone, they then paused the process at the right time by blocking a molecule called vascular endothelial growth factor (VEGF). And it seemed to work.

“What we ended up with was cartilage that is made of the same sort of cells as natural cartilage with comparable mechanical properties, unlike the fibrocartilage that we usually get,” says Chan. “It also restored mobility to osteoarthritic mice and significantly reduced their pain.”

The process also worked in mice with human tissue, suggesting that the treatment would be viable in humans. Investigating that is the planned next step for the team. If so, the first human clinical trials could be done on small joints like thumbs, before moving up to bigger ones like knees.

There's no shortage of research into repairing or regenerating cartilage. Other teams are investigating ways to 3D print hydrogels for knee replacements, culturing new cartilage from cells taken from a patient's nose, or replacing damaged cartilage with new materials like "bioglass" that stimulate the regrowth of the tissue.

The new study was published in the journal Nature Medicine.

Source: Stanford University