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More About Stem Cells and PRP For Osteoarthritis

By Nathan Wei
Mar 11, 2009
A number of methods have been used to repair of cartilage damage. The first is osteochondral transplantation, which involves taking a plug of cartilage from a non-weight bearing area and placing it into a defect in a weight-bearing region. The second is microfracture. In this procedure, a surgeon will drill a number of small (2 mm diameter) holes into the cartilage until bleeding from the bone marrow occurs. The theory is that stem cells from the bone marrow will "leak out" and heal the cartilage damage. The final method is the use of autologous stem cell implantation with or without the assistance of a scaffold matrix to hold the cells.

The problem is that all these techniques have been used to treat focal cartilage lesions and not osteoarthritis. Also, recuperation from the first two procedures (chondral plug and microfracture) is exceedingly long.

Osteoarthritis lesions are generally large and unconfined and as a result may not hold onto chondrocytes (early cartilage cells) long enough for them to repair the damage.

Of the three methods described above, the one that seems to be garnering the most interest lately is autologous stem cells.

Results from a number of uncontrolled studies seem to show that stem cells can be harnessed to repair and possibly regenerate cartilage damage in OA.

There are three types of stem cells that have been used in research. The first type is embryonic stem cells. These have the advantage of being the cells that probably can grow the quickest. Unfortunately, there is the theoretical possibility that there might be unregulated growth, ie. cancer. Also, some have raised ethical concerns.

The second type is donor mesenchymal stem cells. These are cells that are obtained from a human volunteer, and then grown in a lab. They have the advantage of numbers. The concentration of stem cells can reach anywhere from 20-50 million stem cells. The disadvantage is the possibility of rejection reaction and also the possibility of transmission of infection.

The final type is autologous stem cells. These are cells harvested from the patient. A large amount of bone marrow is aspirated from the iliac crest of the hip. The bone marrow is then concentrated using a special technique in order to obtain the stem cells.

Duke researchers have recently reported on their findings that stem cells obtained from the fat pad behind the kneecap can be reprogrammed to become cartilage cells. This research is preliminary but is worth noting.

Other theoretical problems and questions regarding the use of autologous stem cells include the following:

* Inability to get enough stem cells from the host
* The relative weakness of older stem cells to multiply and divide
* The possible metabolic abnormality in stem cells taken from a patient with osteoarthritis that might make them more susceptible to degrading earlier
* The inability to stimulate the stem cells to grow
* The best type of matrix to use to "house" the stem cells so they have a place to grow

Recent technological advances have enabled us to address these questions. Through the use of special techniques, harvesting a significant volume of bone marrow aspirate, then concentrating it into a small volume containing anywhere from 1-5 million stem cells has been easily accomplished.

While older stem cells may not have the growth potential of younger ones, they do appear to function well enough to regenerate connective tissue. Still, it is probably wise, in the patient selection process, to exclude patients above a certain age.

There is no convincing evidence that the stem cells obtained from patients with osteoarthritis contain a metabolic defect that would render them ineffective. Nonetheless this area requires more research.

Stimulation of stem cell growth requires the use of growth factors that will bind to the tyrosine kinase receptors on the surface of stem cells. Once the receptors have been stimulated, a signal is sent to the nucleus of the stem cells leading to cell growth and proliferation.

The best "stimulant" appears to be platelet rich plasma which is easily obtained from a patient's peripheral blood. Platelet-rich plasma (PRP) contains platelet-derived growth factor, transforming growth factor-B, fibrinogen, IL-1, epidermal growth factor, vascular endothelial growth factor, and adhesion molecules.

This is a potent soup of protein messengers that readily attach to stem cell surface receptors.

A number of different matrices have been used and this area is still being explored. The major logistical problem is creating a matrix that is biocompatible, biodegradable, and easily instilled.

At our center we use a mixture of calcium chloride and thrombin to create a gel that stem cells are bound to.

The joint is prepared using a specific approach designed to induce a local inflammatory response at the site to be healed. Autologous stem cells, PRP, and the matrix are then introduced carefully using ultrasound needle guidance.

To date, clinical response has been excellent.

Autologous stem cells provide an attractive option for both osteoarthritis patients and their physicians. Combining stem cells and PRP appears to be physiologically sound and more importantly, effective. This procedure holds much promise for Baby Boomers who wish to remain active.

For more information about stem cells and PRP, contact the Arthritis and Osteoporosis Center of Maryland at (301) 694-5800.
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