THE CUTTING EDGE IN THE TREATMENT OF INJURIES AND ARTHRITIS
ARE WE CLOSE TO THE HOLY GRAIL?
Autologous Regenerative Therapies a.k.a Orthobiological treatments
By Steve A. Mora, M.D.
Over the last 5 years there has been a surge of information regarding the use of non-operative therapies which harness the body’s own healing capacity to relieve or heal from injuries. Some of these treatment have been called blood therapies because they utilize some component of a patient’s own blood. These treatments include Platelet-Rich Plasma, Mesenchymal Stem Cell injections, amniotic tissue, Hyaluronic Acid injections, and Orthokine. As a whole these therapies are being called Autologous Regenerative Therapies. A whole new sector in the treatment of pain is emerging called “Orthobiologics”.
It’s quite possible that we are entering the era where the solution to arthritic pain or injury is no longer found by way of the scalpel but instead within our cells that have the capacity to heal.
Platelet Rich Plasma (PRP) is by far the most common regenerative treatment. The media attention on celebrities and superstar athletes has helped boost the popularity and awareness of these agents. The reality is that star athletes are not just getting PRP. There are other novel biological therapies available.
Why has there been such a surge in popularity of these treatments? There are numerous factors including the fact that surgical procedures are not as effective as we once thought, recovery after a surgery can be lengthy and patient are more educated about cutting edge medical advances. Also in general I think people, especially athletes, do not want surgery. Patients are more interested in biological treatments and prevention. There have been advances in molecular research which as advanced our knowledge of the stages of injury, cell death, chondral degeneration and the onset of post traumatic arthritis. There is also a financial issue. These treatments are usually not covered by insurance so patients with resources are paying for them cash up front. Some treatments go for as much as 10-15 thousand dollars. The industry is aware of this so there can be is a push to offer patients a novel treatment even though the evidence is not strong that it will work.
The goal of this article is to touch on the more common Autologous Regenerative Therapies such as PRP and stem cell treatment. My goal is to answer the questions I frequently get asked in my own practice.
PLATELET RICH PLASMA
Platelet Rich Plasma (PRP) therapy appears to be a promising solution to accelerate healing of tendon injuries. Blood is made of RBC (Red Blood Cells), WBC (White Blood Cells), Plasma, Water, Clotting Factors, Antibodies and of course Platelets. Platelets were initially known to be responsible only for blood clotting however it was become clear that they do more than help create a blood clot. Cumulatively platelets and their growth factors may accelerate tissue and wound healing capacity. The process is simple: Your blood is drawn and put into a test tube. The blood is put through a series of centrifuge spins to increase the baseline concentration of platelets. The layer with the platelets is drawn out, put into a syringe and injected into the desired area. The injection is sometimes done with ultra-sound or fluoroscopy x-ray guidance. Often times a series of injections are necessary to optimize healing. The theory behind PRP is that it will ignite or initiate the healing response in an area that is stubborn to heal such as a torn tendon. PRP can be injected in combination with hyaluronic acid or alone. It has been shown to be effective for the treatment of mild to moderate arthritis of the knee. For the treatment of knee arthritis some doctors may recommend a total of 3 PRP/HA injections. Each injection can be done 2 weeks apart. The bottom line is that we do not know how many treatments are required to make a difference. Pain improvement is usually not immediate. It can take up to 3-4 weeks to feel better.
In some cases of knee arthritis which involves significant loose debris I will recommend a simple knee arthroscopy to remove large loose debris and flush out the inflammatory effusion. An option to do mesenchymal stem cell treatment or PRP/HA injection treatment can be made. Patients who have suffered an acute meniscus tear might also benefit from PRP treatment. In this particular scenario the body is already trying to heal an acute injury so a boost with PRP can theoretically optimize this affect.
Viscosupplementation, a.k.a. Hyaluronic acid (HA) injections, is a treatment option that is FDA approved for arthritis of the knee. Due to its success, some physicians have been using it “off label” (not FDA approved) for the treatment of arthritis of other joints such as the hip and ankle. Hyaluronic acid injections are recognized by most insurance carriers. The treatment involves injecting a gel like substance into the joint cavity. In order to improve accuracy the injection is sometimes performed using ultra-sound or fluoroscopy x-ray guidance. Once in the joint the gel-like fluid mimics natural components of the joint and cartilage called “hyaluronic acid”. The fluid provides an initial lubricant and or “cushion” effect resulting in pain or grinding reduction. In time it will get absorbed into the joint surface potentially generating a more durable cartilage. It is therefore more effective for joints which still have some cartilage remaining. Due to its anti-inflammatory effect, HA may even play a role in diminishing the risk of post traumatic arthritis after articular fractures. Common brands of HA include Synvisc, Orthovisc, Supartz, and Euflexxa. Visco- supplementation injections are usually performed once a week for 3 consecutive weeks. In some cases we can do a large of Synvisc however not all knees can accommodate so much fluid. Some patients tend to do better with one brand versus another. For this reason we sometimes switch the brand if the first series of injections did not help much. It can be repeated every 6 months or less. There really is no down side to injecting HA in a joint. For the treatment of mild or moderate arthritis I have been injecting a cocktail containing PRP and HA. Studies have shown that this combination of treatments is more effective than injecting HA alone.
MESENCHYMAL STEM CELLS: BONE MARROW CONCENTRATE INJECTIONS AND ADIPOSE TISSUE MESSENCHYMAL CELLS
Mesenchymal stem cells (MSC) can be readily obtained from the pelvis and from your own adipose tissue (fat) around your belly and waist. The benefit of Adipose Tissue MSC versus Bone Marrow MSCs is not certain. Doctors tend to use the one which they feel comfortable harvesting. Mesenchymal stem cells have potent anti-inflammatory effects and growth factors. Mesenchymal stem cells are different than embryonic stem cells because of their ability to only form particular tissue such as cartilage, muscle, and tendons. These adult mesenchymal stem cells help to maintain our body’s continuous cycle of repair and healing of injuries. As we get older the concentrating of MSC is thought to diminish and as a consequence it becomes harder for us to recover from injury and/or damaged joints. Mesenchymal stem cell injections are being used to accelerate healing, and decrease pain in moderate to severe osteoarthritis and for acute injuries. The theoretical benefit of MSC over PRP is that you are getting a much higher concentration of growth factors and more anti-inflammatory potential.
The process of obtaining these powerful regenerative cells is similar to PRP which also requires 2 steps. Part one requires your doctor to aspirate your bone marrow or to perform a mini liposuction procedure to get fat. Both can be done as an office procedure under local anesthesia. Part 2 involves concentrating the cells using special centrifuge equipment and then injecting the acquired MSC into the desired area. In order to optimize the healing and pain reduction potential, MSC can be combined with PRP. Although the MSC has some platelets, a PRP preparation from a simple blood draw will increase the total number of platelets being injected. The patient is able to go home the same day of the injection. A PRP booster can be given 6-8 weeks after the MSC injection. Some doctors are doing Bone Marrow Concentrate immediately after a lavage and debridement surgery for patients with severe OA of the knee. There has been a surge in interest and in research on this topic however there is still minimal evidence that it is better than HA injections or steroid injections alone. There is growing amounts of empirical evidence (basically patient and doctor testimonials) showing that it helps. Compared to PRP this treatment is more involved, takes more time, requires more equipment and therefore is more expensive. Patients who have had bone marrow conditions such as cancer or bleeding disorders are not candidates for bone marrow harvesting.
ALLOGENEIC MESENCHYMAL STEM CELLS
Allogeneic mesenchymal stem cells are derived from the human placental tissues. Allogeneic means that it comes from another human being therefore it is technically not a “autologous” regenerative therapy. Placental tissues are a rich source of collagen, elastin, fibronectin, mesenchymal stem cells and growth factors that can support tissue repair and regeneration. Amniotic tissue is can be harvested at the time of child birth from prescreened donors. This amniotic tissue/fluid is harvested without harming the baby. There are no baby cells in the preparation; its the amniotic tissue membrane that is left over after child birth. The amniotic cells have low immunogenicity (should not lead to rejection). These tissues can be obtained from a small number of companies freeze dried or frozen. The amniotic tissue is processed by fragmenting it into fine particles which can be injected into an arthritic or injured area. A recent scientific paper published in January of 2014 out of University of Southern California showed a benefit in pain control and possibly in regeneration of meniscus tissue after knee arthroscopy for meniscus tears. The tissue is expensive therefore the procedure can be more expensive than PRP/HA or Bone Marrow Concentrate/Adipose tissue. We also do not know how many injections will help. We do not know if it will actually regenerate cartilage or meniscus. If it is only decreasing pain, a PRP/HA or MSC injection may be just as effective.
Orthokine is another autologous blood based treatment invented by a German orthopaedic surgeon named Dr. Peter Wehling. The procedure involves removing some of the patient’s own blood, incubating the blood at a slightly raised temperature. Raising the temperature while the blood sits on glass beads increases the concentration of a natural anti-inflammatory known as Interleukin-1 receptor antagonist. The warmed up blood is then spun and the isolated component injected into the patient’s painful area. The procedure is not FDA approved therefore it is not advertised. In the US there are only a couple of centers which have been licensed by Dr. Wehling to perform the procedure and it is referred to as Regenokine. Kobe Bryant popularized the Orthokine treatment after he traveled to Germany in 2012. Some people refer to the treatment as the “Kobe procedure”. There is minimal scientific evidence that it works however there are many patient testimonial that it can help. Orthokine has been studied at the Universtity of Pittsburg. It is considered safe. The cost has been reported to be in the $8000.00 range per treatment.
To summarize there is a huge void in the treatments available for patients who have pain due to degenerative arthritis or cartilage injuries. So what do you do if you are under 50 and have had a steroid injection and maybe some hyaluronic acid for your arthritic knee pain? Do you live with the pain and maybe have surgery some day in the future when it is really bad? What do you do if you are a high level athlete with a meniscus tear or pain due to sports related injuries and you need to compete in a month or two? These are the dilemmas we are seeing every day. This is why these treatments should be looked at a bit more closely. This biological approach to treating injuries is very exciting and holds great promise. We just might be a step closer to the Holy Grail of treatments, i.e. a treatment that can help heal, regenerate and prevent future degeneration.
Steve A. Mora, M.D.
Orthopaedic Surgeon specializing in sports medicine, knee, elbow and shoulder.
Orange County Orthopaedic Surgeon
I focus on injuries related to sports related trauma, combat sports and soccer injuries. I perform mesenchymal stem cell injections derived from bone marrow and platelet pure plasma. For appointments please call 714 639-3750. For info regarding my practice you can also visit me on youtube.com
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