Spurring Stem Cells to Rebuild Cartilage

Researchers have demonstrated modest progress towards the goal of making the body's existing cell populations rebuild damaged cartilage in situ:

A small molecule dubbed kartogenin encourages stem cells to take on the characteristics of cells that make cartilage, a new study shows. And treatment with kartogenin allowed many mice with arthritis-like cartilage damage in a knee to regain the ability to use the joint without pain. ... The new approach taps into mesenchymal stem cells, which naturally reside in cartilage and give rise to cells that make connective tissue. These include chondrocytes, the only cells in the body that manufacture cartilage.


"In the blue-sky scenario, this would be a locally delivered therapy that would target stem cells already there," says study coauthor Kristen Johnson, a molecular biologist at the Genomics Institute of the Novartis Research Foundation in San Diego. Johnson and her colleagues screened 22,000 compounds in cartilage and found that one, kartogenin, induced stem cells to take on the characteristics of chondrocytes. The molecule turned on genes that make cartilage components called aggrecan and collagen II. Tests of mice with cartilage damage similar to osteoarthritis showed that kartogenin injections lowered levels of a protein called cartilage oligomeric matrix protein. People with osteoarthritis have an excess of the protein, which is considered a marker of disease severity. Kartogenin also enabled mice with knee injuries to regain weight-bearing capacity on the joint within 42 days.

As a long term goal for tissue engineering, controlling existing cell populations sufficiently well to rebuild lost or damaged structures in the body is preferable to strategies that involve surgery - such as, for example, building cartilage outside the body and then implanting it. Both avenues are under development at this time.

One consequence of an increased focus on controlling stem cells in the body is that researchers must find ways to reverse the stem cell decline that comes with aging. If stem cell populations are generally less effective, then therapies based on directing those cells may be of limited benefit. Given that most of the regenerative therapies we can envisage will be of greatest use to the elderly, the people who bear the most damage and bodily dysfunction, and who are generally the wealthiest portion of the population, there is a strong financial incentive to find ways to build working therapies for that market. This is why I see the regenerative medicine community blending in at the edges with the longevity science community in the years to come - many of the goals are much the same.


I have been reading about the possibilities of therapy for osteoarthritis in the knees using Kartogenin. Unfortunately, any research seems to be limited to mice at the moment. I am hoping to be able to benefit from this type of intervention, but at 73 years of age, I am afraid that I will die of old age before it becomes available. Do you have any idea of how long it will be before human subjects will be considered for such therapy? Any information in this matter will be appreciated.

Posted by: Keith J. Trawick at September 23rd, 2012 5:25 PM

Does a bone marrow injection in a knee facilitate cartilate/meniscus growth?

Posted by: giuseppe lama at January 12th, 2014 8:34 AM
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