Research on stem cells is leading scientists to investigate the possibility of cell-based therapies to treat disease, which is often referred to as regenerative medicine.
Stem cells have two important characteristics that distinguish them from other types of cells. First, they are unspecialized cells that renew themselves for long periods of time through cell division. The second is that under certain physiologic or experimental conditions, they can be induced to become cells with special functions.
There are two different sources of stem cells. Embryonic cells are derived from fetal tissue and are a source of great controversy. Adult stem cells (ASC), on the other hand, are found in normal people.
ASC can renew themselves, and can differentiate to yield the major specialized cell types of the tissue or organ. Their primary role in a living organism is to maintain and repair the tissue in which they are found.
Research on adult stem cells has recently generated a great deal of excitement. Scientists have found adult stem cells in many more tissues than they once thought possible. This finding has led scientists to ask whether adult stem cells could be used for transplants. In fact, adult blood forming stem cells from bone marrow have been used in transplants for 30 years. Certain kinds of adult stem cells seem to have the ability to differentiate into a number of different cell types, given the proper conditions.
Bone marrow derived stem cells give rise to a variety of cell types: bone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and other kinds of connective tissue cells such as those in tendons.
According to information from the National Institutes of Health, “One of the fundamental properties of a stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. Unlike muscle cells, blood cells, or nerve cells-which do not normally replicate themselves-stem cells may replicate many times.
When cells replicate themselves many times over it is called proliferation. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. “
The process by which unspecialized stem cells become specialized cells is called differentiation. Adult stem cells typically generate the cell types of the tissue in which they reside. A blood-forming adult stem cell in the bone marrow, for example, normally gives rise to the various types of blood cells such as red blood cells, white blood cells and platelets. Until recently, it had been thought that a blood-forming cell in the bone marrow could not give rise to the cells of a very different tissue.
However, a number of experiments over the last several years have raised the possibility that stem cells from one tissue may be able to give rise to cell types of a completely different tissue. This phenomenon is referred to as “plasticity. “
Two research presentations this past year shore up the promise of stem cells in arthritis. First, research presented in April 2008 at the UK National Stem Cell Network Annual Science Meeting in Edinburgh offered hope that stem cells may be harnessed to repair the damaged cartilage that is one of the main symptoms of osteoarthritis.
On a related note, scientists at Cardiff University in the United Kingdom have successfully identified stem cells within articular cartilage of adults, which have the ability to become chondrocytes, cells that make up cartilage. The team has even been able to identify the cells in people over 75 years of age.
Lead researcher Professor Charlie Archer from the Cardiff School of Biosciences said:
”This research could have real benefits for arthritis sufferers and especially younger active patients with cartilage lesions that can progress to whole scale osteoarthritis. “
According to Dr. Nathan Wei, a rheumatologist and clinical investigator in Frederick, Maryland, “We are focusing our efforts on adult autologous stem cells (”autologous” meaning derived from the patient himself). These cells are present within a patient’s bone marrow. Once we obtain the stem cells, they need to be concentrated using special techniques in order to secure the number of stem cells per unit volume needed. We have been using this treatment, combined with growth factors obtained from other cells, for both osteoarthritis of the knee as well as the hip. Preliminary results using both subjective as well as objective measures show much promise. If these results are validated, the springtime of your life when it comes to weight-bearing joints may actually be 55-75. ”
Nathan Wei, MD FACP FACR is a nationally known board-certified rheumatologist. For more info: Arthritis”>http://www. arthritis-treatment-and-relief. com/arthritis-treatment. html”>Arthritis Treatment and Tendonitis Treatment Tips
In the last few years, a number of methods have been developed to repair cartilage damage. These include osteochondral transplantation, microfracture surgery and autologous chondrocyte (cartilage cell) implantation.
A feature common to all of these techniques is that they are limited to the repair of focal lesions. Patients with OA are excluded from treatment.
OA cartilage lesions are usually larger and unconfined and so do not provide an appropriate environment for chondrocytes to be retained long enough to build a framework (matrix).
So. . . successful repair of OA cartilage damage is dependent on the ability to form a matrix within the joint.
Effective cartilage engineering protocols have already been developed in which chondrocytes in young animal models have been shown to be effective in creating cartilage.
Generating cartilage using adult human cartilage cells is far more challenging. Older OA patients have cartilage that is less responsive to stem cell stimulation and their stem cells seem to respond less well to the usual growth factors.
There are three potential avenues for obtaining stem cells. The first are embryonic stem cells which have the attraction of being relatively pristine. However, political and ethical interests have made this source of stem cells unobtainable. Plus, there is the theoretical possibility that theses stem cells may grow unchecked leading to unregulated growth, ie cancer.
A second source are mesenchymal stem cells grown in a laboratory from normal volunteers. While carefully screened for diseases and genetic problems, these stem cells do carry the potential for possible rejection reactions.
Finally, the last source and the one that seems to have the most promise- at least for now- are autologous stem cells. These are stem cells harvested from the iliac crest of the patient.
Autologous stem cells provide an attractive option for osteoarthritis patients and their clinicians. However it must also be recognized that autologous therapies are expensive. Ideally, it would be good to treat the specimen obtained from the iliac crest to growth factors, cytokines, and chemokines, to stimulate an increase in the number of stem cells.
However, both governmental regulations as well as sterility concerns preclude this step.
In addition, the search for better matrix production to allow stem cells a “home” to grow in and multiply is still being studied.
There have been a few clinical trials that have demonstrated some promise. The first comes from Murdoch University in Australia.
Working with Australia’s adult stem cell company, Mesoblast Limited (ASX:MSB), the University’s pre-clinical trials of Mesoblast’s patented adult stem cells had shown the therapy to significantly protect cartilage against damage in knee osteoarthritis.
The project’s principal investigator, Professor Rick Read stated, “We are delighted with the significant cartilage protective effects of Mesoblast’s allogeneic (donor unrelated) cells in our large animal model of knee osteoarthritis, without any adverse events of the cells at all. “
Mesoblast’s cartilage trials evaluated the effectiveness and safety of the company’s allogeneic adult stem cells to treat osteoarthritis of the knee in 48 arthritic sheep joints.
The results showed that osteoarthritic sheep knee joints receiving Mesoblast’s stem cells had significantly greater thickness of joint cartilage, reduced cartilage breakdown, and greater biomechanical strength three months later than did control joints receiving hyaluronic acid.
In another study, Duke University Medical Center researchers have “reprogrammed” adult stem cells taken from a small deposit of fat behind the kneecap into functioning cartilage, bone, or fat cells that could potentially be grown into replacement tissues for osteoarthritis.
The research team has provided evidence that stem cells taken from different adult sources have the potential to be transformed into multiple specialized cell types.
In the current study, the researchers took the fat pads from patients whose knee joints were removed during total joint replacement surgery. The fat pad is a dense structure behind the patella, or kneecap that is unlike typical fat tissue found throughout the body.
They were able to isolate and grow adult stem cells from this tissue.
According to scientists at Cardiff University, stem cells identified in their studies can be turned into cartilage cells (chondrocytes) in huge quantities. This may mean that limitations in cartilage transplants, in which healthy cartilage cells are collected and transplanted into a damaged joint, could be overcome.
However, despite recent media reports that heralded the identification of these stem cells as a breakthrough in the treatment of osteoarthritis, this research is currently only being considered to treat people with limited cartilage damage only.
Dr. Nathan Wei states, “Our current understanding of stem cell biology is obviously not where it needs to be. However, early work at our center using autologous stem cells obtained from iliac crest bone marrow and then concentrated has shown very promising results in patients with osteoarthritis of the knee. It is important to comment on the fact that prior to introduction of the stem cells, irritation of the cartilage and adjacent capsule is important to initiate an inflammatory response which then leads to cell proliferation which is an essential part of healing and subsequent cartilage regeneration. “
Dr. Wei adds, “For sure, though, I feel that this approach which is relatively painless will prove to be more effective than other therapies we currently have for osteoarthritis. “
For more information about stem cells and osteoarthritis, call the Arthritis and Osteoporosis Center of Maryland at (301) 694-5800.
Nathan Wei, MD FACP FACR is a nationally known board-certified rheumatologist. For more info: Arthritis”>http://www. arthritis-treatment-and-relief. com/arthritis-treatment. html”>Arthritis Treatment and Tendonitis Treatment Tips
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