Developing effective treatments for osteoarthritis and other problems including autoimmune diseases, through the cutting edge discipline of regenerative medicine, is a long-term project. It involves many years, perhaps decades of intense research; millions of dollars of funding and, once the human trial stage has been reached, thousands of patients. To the person suffering with osteoarthritis, progress can seem slow, especially when their condition has deteriorated to a stage whereby a hip and/or knee replacement operation is presented as the only option.
However, every now and then there is a hint of a breakthrough in osteoarthritis research and one such moment occurred only recently in France where a small stem cell trial released some modest but positive outcomes. The results may not have been conclusive but, from the patients’ perspective, they were promising enough to convince them all to cancel their pending knee replacement operations!
Osteoarthritis (or more pedantically, osteoarthrosis) is the most widespread of the different forms of arthritis and the most common joint disease. It is thought to have an autoimmune basis, and it involves the deformation and breakdown of cartilage in the joints and the body’s reaction to that damage leads to pain, inflammation and disability. Healthy hyaline cartilage, which lines bones in joints and allows them to glide over one another, is a substance formed of proteoglycan aggregates and collagen and is smooth and uniform. Gliding is facilitated by a thin layer of synovial liquid. During osteoarthritis, this cartilage becomes rough and thins in places. As the body tries to repair the damage it creates further problems, for example forming bony spurs (osteophytes), producing excess synovial fluid and causing ligaments to thicken and contract.
The etiology of osteoarthritis can be due to a number of factors including genetics, obesity, overuse of the joint, injury and even an imbalance in the levels of minerals and hormones in the blood, sometimes caused by co-existing metabolic disorders. As a degenerative disorder, osteoarthritis worsens with age although there are a wide range of interventions that can tackle some of the symptoms, mainly pain and inflammation. A few of these include acetaminophen (Tylenol), traditional non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, diclofenac and naproxen, COX2 inhibitor type of NSAID; opioids ,such as codeine or tramadol, capsaicin cream, corticosteroid injections or visco-supplementation through regular injections of hyaluronic acid, an important chemical found in the lubricating synovial liquid.
Stem Cells: From Repair to Regeneration
The biochemistry within the knee joint is complex and involves the action of both metabolic and catabolic factors. In osteoarthritis, pro-inflammatory molecules and fibroblast-like synoviocytes within the synovial fluid proliferate and create an inflammatory environment with apoptotic (destructive) processes causing the degradation of the cartilage at a much faster rate than it can be replaced. In response to this pathogenesis, researchers have been focusing on tissue engineering and cell therapy, looking at ways to stabilize symptoms by blocking the agents of inflammation and to improve the health of the cartilage either through repair or regeneration.
While stem cell research is still in its early stages, surgical interventions have centered on non-regenerative cartilage repair through the allogenic transplant of cartilage or the autologous transplant of differentiated cartilage tissue. When successful, this can restore some function and alleviate symptoms but it is a temporary measure as the newly transplanted cartilage is often of poor quality and will still be subject to the catabolic processes that are at the heart of osteoarthritis. What is needed is a progression from tissue transplantation to tissue repair and regeneration, and this is where stem cell deployment come in.
The power of stem cells lie in their ability to differentiate into many different types of cell while producing adequate numbers of stem cells maintain the back-up pool. From the totipotent stem cells of the human embryo (ESCs) to the multi-potent stromal stem cells, able to form cells from within a specific tissue layer, these specialized units offer huge potential for the eventual ability to regenerate the tissues involved in cartilage formation, in particular the chondrocytes which both form and create the cartilaginous matrix. Chondrocytes originate from the mesoderm layer of the human body as do bone, fat and blood cells. All of these can be produced by mesenchymal stem cells (MSCs) which are abundant and easily extracted from the body, found in the bone marrow, adipose (fat) tissue and in the synovial fluid of the knee joint itself, the latter being highly proliferative.
While much stem cell research is ex vivo with stem cells harvested and cultured in a laboratory setting, often to test the effect of various growth factors on chondrogenesis, some in vivo therapies have progressed from animal models and are now beginning to form early stage trials in human patients.
A Recent Breakthrough in Autologous Stem Cell Trials?
In May 2016, Stem Cells Translational Medicine, a journal specializing in facilitating the translation of leading stem cell research into reputable trials and treatments, published the results of a French trial led by auto-immunology specialist Christian Jorgensen M.D. Ph.D., head of the clinic for osteo-articular disease in Lapeyronie University Hospital, Montpellier. The early trial involved just 18 patients, men and women between the ages of 50 and 75 years. To qualify for inclusion, the participants must have been living with severe knee osteoarthritis for at least a year prior to the trial (which began in April 2012).
The procedure involved a simple single intra-articular injection of adipose-derived stromal stem cells (ASCs) into the knee. ASCs are a type of MSC obtained from adipose (fat) tissue, normally through liposuction. The patients were divided into three groups: one group were injected with a low-concentration dose of stem cells, another with a medium-concentration dose, four times as potent as that given to the ‘low’ group and a third with a high-concentration dose, five times as potent as the ‘medium’ group received.
Although all three groups reported favorable outcomes after six months in terms of pain reduction, decreased inflammation and better mobility, it is important to point out that the only statistically significant improvements came from the first group who had had the lowest dose of stem cells. Of course, such a small sample of patients is unlikely to yield much in the way of meaningful quantitative data but it is interesting that all of the patients involved in the trial decided to cancel their upcoming knee replacement operations. The results of the next trials should be more informative; these are taking place across 20 European medical centers and involve hundreds of osteoarthritic patients.
Fortunately, for those osteoarthritis patients who may be ineligible for clinical trials or unable to take part, there are numerous high quality experimental stem cell treatments available that utilize a similar method to harvest and re-introduce a patient’s own MSCs via injection. As the process of obtaining autologous stem cells maintains a closed system and employs no laboratory modifications, it is not in violation of FDA guidelines. Patients should however be sure to carefully check the credentials of the medical team and the center facilities before agreeing to treatment as protocols and quality can vary.
The investigational use of adipose-derived stem cells for the treatment of orthopedic and joint diseases is a current specialization of the Mississippi Stem Cell Treatment/ Gulf Coast Stem Cell and Regenerative Medicine Center. If you are interested in finding out more about how we may be able to help you with your osteoarthritis or other autoimmune condition, please call us on (866) 885 4823. Further information is also available on our website at: http://www.gulfcoaststemcell.com