Bone scraping on bone — you can practically feel the excruciating pain just thinking about it. Sadly, that’s what happens to people suffering with osteoarthritis (OA), a degenerative joint disease. Except for joint replacement surgery, no cure exists and the available medicines only work on the symptoms, pain and swelling, and not the underlying cause. On top of that, long-term use of the drugs carries potential serious side effects including gastrointestinal bleeding and increased risk of a heart attack.
The statistics on this disease are just plain dreadful. It’s estimated that 250 million people worldwide have osteoarthritis of the knee. And 43 million globally have a moderate to severe form of OA. Based on a 2011 analysis, OA was the second-most expensive condition treated in U.S. hospitals amounting to nearly $15 billion in costs.
Imagine the increased quality of life for millions of people around world and the enormous health care savings if a cure were developed?
A study published on Tuesday in Stem Cells Translational Medicine may turn the tide toward a lasting treatment for osteoarthritis. A research team at the University of Manchester in England reported that they repaired knee joints in animal studies by implanting cartilage cells derived from human embryonic stem cells (hESC).
In a healthy joint, the ends of the bones are capped with cartilage, a hard but slippery substance that allow the bones to slide smoothly against each other. The cartilage also acts as a shock absorber for the joints when the body is in motion.
This protective tissue in the joint gradually degrades in OA. The degradation in some cases is initiated by an injury even a minor one. Because cartilage lacks blood vessels, it doesn’t receive nourishment from the blood and is no good at repairing itself. And so eventually the bones at the joint are exposed and begin to rub against each other leading to severe pain, swelling, and reduced mobility.
In previous studies, the University of Manchester research team led by professor Sue Kimber, devised a method for specializing human embryonic stem cells into so-called chondroprogenitors, or cells with the potential to form cartilage.
The team implanted the cells into the knee joints of rats modeled with OA-like defects to test their ability to repair cartilage. By four weeks after the implant, the treated rats began to show signs of cartilage healing compared to an untreated group. By 12 weeks the treated joints revealed a shiny smooth surface characteristic of healthy cartilage while the untreated group still showed rough misshapen cartilage, a hallmark of OA. In a press release, Professor Kimber put these results in perspective:
“This work represents an important step forward in treating cartilage damage by using embryonic stem cells to form new tissue, although it’s still in its early experimental stages.”
Compared to this preliminary hESC work, the use of cartilage-producing cells derived from adult stem cells is already being tested but the source material is limited making that method ultimately very costly and not scalable. hESCs, on the other hand, can be grown in unlimited quantities for large-scale, off the shelf cell therapy for the millions of OA sufferers. If you’re still following along, you might be thinking “but wouldn’t those hESC-derived therapies be recognized as foreign and rejected by the OA patient’s immune system?” That is a serious hurdle, but data from other labs hint at the possibility that cartilage repair may be possible with minimal tissue matching between the donor cells and the patient.
There is also reason to believe the cartilage derived by embryonic stem cells (ESCs) might be superior to that created to-date from adult stem cells. The latter tends to produce a softer form of cartilage than the hard cartilage found in our knees called articular cartilage. Because the ESCs produce cells that are earlier in the development cycle it may be possible to push them to become the sturdier cartilage we want in our knees. CIRM grantee Darryl D’Lima at The Scripps Research Institute has shown that seems to be the case in his preliminary studies.
Finally, a big concern of using hESC derived cell therapies is that some unspecialized cells will remain in the implant with the potential of unlimited growth leading to tumor formation and cancer. But in this study the results were encouraging since no irregular cartilage formation or tumors were seen.
Clearly it’s still early days for a hESC approach to curing OA. But these results are promising enough to draw out this response from Stephen Simpson Director of research at Arthritis Research UK which funded this study:
“Embryonic stem cells offer an alternative source of cartilage cells to adult stem cells, and we’re excited about the immense potential of Professor Kimber’s work and the impact it could have for people with osteoarthritis.”