Biologics

What is platelet-rich plasma (PRP)?

Blood has four main components: red blood cells, white blood cells, platelets, and plasma. Platelets are tiny blood cells that are mainly in charge of blood clotting; they transport over 1,500 proteins responsible for stimulating the proliferation of new cells and collagen (one of the main components of cartilage) and suppressing inflammation and cell death. Plasma is the fluid that carries all the other blood cells. PRP injections aim to deliver a large number of platelets to injured tissues in the hope that they can help an injury heal better and faster. Platelets play a fundamental role in healing because they are a natural source of growth factors (proteins), which are involved in the important stages of tissue healing and regenerative processes. They tell your body to send the proteins needed for regeneration.

How is PRP made?

PRP injections are made from your own blood, which is collected and then centrifuged at varying speeds until it separates into layers. Different types of blood cells have different weights. If blood is treated to prevent clotting and permitted to stand in a container, the red blood cells, which weigh more than the other components, will settle to the bottom; the plasma (liquid) will stay on top; and the WBCs and platelets will remain suspended between the plasma and the RBCs.

To accelerate and refine this process, a PRP machine is typically used to centrifuge the blood. This is carried out to exclude RBCs from the injection solution, as these are detrimental for the joints. Furthermore, recent research has found that too many white cells are also disadvantageous to the joint because they cause more inflammation.

The whole centrifuge process takes approximately twelve minutes and produces a platelet concentration of three to five times that of original plasma. (The number of platelets needed is not well understood, nor which growth factors are more favorable to produce the desired effects.) Immediately prior to the injection, a platelet activator may be added to initiate the clotting process, producing a platelet gel.

What are the outcomes after a PRP injection?

Leukocyte-poor (low white blood cell) PRP has been shown in multiple clinical trials to be more effective than placebo, steroid, and gel injections for the treatment of mild to moderate osteoarthritis symptoms. As with other biological injections, multiple studies have concluded that better results can be achieved in early versus advanced osteoarthritis. When compared to corticosteroid injections for advanced knee osteoarthritis, the magnitude of improvements tend to be greater in the PRP group.

Regarding the number of injections needed, recent literature has shown that a minimum of two injections was more successful in treating the symptoms than a single shot for patients with early osteoarthritis. For patients with advanced osteoarthritis, multiple injections did not significantly improve the results of patients. Researchers from Europe have suggested that the average duration of symptom relief after an injection is nine months and that yearly injections could be beneficial to maintain the effects in a consistent manner. Nevertheless, although multiple studies have shown PRP to improve symptoms, no cartilage healing has been demonstrated in any studies.

A combination of a PRP injection with an HA gel injection may have an even more powerful effect, by enhancing the potential of both injections to attract your own body-healing proteins. Furthermore, some studies reported that the combination of HA and PRP could inhibit inflammatory symptoms even more. A recent clinical trial comparing PRP alone, HA alone, and both in combination demonstrated that combining HA and PRP resulted in a significant decrease in pain and functional limitation when compared to HA alone when patients were evaluated one year after the treatment, and significantly increased physical function at one and three months when compared to PRP alone.

A number of studies have also been conducted to assess the effects of PRP on the treatment of tennis elbow (lateral epicondylitis), golfer’s elbow (medial epicondylitis), ACL tears, meniscus tears, rotator cuff tears, Achilles tendon injuries, patellar tendinitis, and other sports-related injuries. The results of these studies show promising early results, and you should discuss the specifics with your physician.

Most of the possible adverse effects associated with PRP injections are not specific to PRP but to every biological injection. They include pain, stiffness, fainting, dizziness, headache, nausea, gastritis, sweating, and rapid heart rate, which usually resolve within days. Risk of infection is a concern as with any injection that penetrates the joint. PRP preparations that have higher concentrations of white cells are more prone to result in inflammatory reactions

Stem Cell Treatment

Most patients are interested in stem cell treatments because of their potential as a novel treatment for a number of health issues. Although this is an exciting treatment field, it’s an emerging and rapidly developing one, so far mainly driven by idealized outcomes that have not been widely realized in clinical practice.

Stem cells are a group of cells from your own body that have the possibility to become any type of cell in the future depending on the signals they receive. When you are conceived, you are composed of many stem cells that end up forming your organs and different tissues. This group of cells is powerful when you are born, and at that time their healing potential is strong. Throughout life, organs and tissues are constantly changing their cells; dead cells are replaced by new cells derived from your own stem cells. As you age, the number of stem cells you have diminishes, stem cells start to lose their potential to regenerate, and aging signs become evident. Besides having a regenerative potential, stem cells are powerful signaling cells: this means they can regulate the body’s inflammatory response, and they can organize which proteins are needed in each case. Because of this ability, stem cells have been proposed as a potential regenerative source for patients with osteoarthritis, which has yet to be proven in vivo.

For treatment purposes, stem cells can be extracted from blood, bone marrow, fat, muscle, and virtually every tissue in the body. Research efforts are currently focused on determining the ideal source for harvesting these cells.

One method of stem cell treatment is a same-day procedure in which the cells are extracted, concentrated, and then injected in the body. The most well-known procedure is a bone marrow aspirate concentrate. This procedure is FDA-approved and requires only minimal manipulation of the harvested cells (no chemical addition). The number and type of cells present within the aspiration, however, is generally not optimal; it has been found that in bone marrow aspirates the amount of cells present is 0.001%. Also, these cells may not have the best regenerative potential; the harvesting may yield a mix of stem cells with great, medium, and poor regenerative potential. Bone marrow aspirate has a potential to diminish inflammation even further (when compared to PRP) because of the presence of interleukin-1 receptor antagonist, which is a powerful blocker of inflammation within the joint, which could explain the relative speedy action after the bone marrow injection.

True stem cell therapy may have more promise, but there is limited evidence and it is not FDA approved. Therefore, it cannot be performed in the United States if it is not within a clinical trial. Stem cell therapy involves harvesting and isolating the stem cells with the greatest potential to grow, then multiplying them by sequential culturing processes that will produce millions of stem cells with the greatest regenerative potential. All of these potential benefits have been proven mostly outside the body (in the laboratory), although the results and their safety profile have not been completely established in humans. That is the reason why they are not yet approved by the FDA as of now.

Despite the potential benefit of stem cell use, the information available about stem cell injection outcomes in human patients is limited. The overall reported outcomes are decent, with a relatively safe profile. No major adverse events have been reported. Just a few randomized clinical trials have looked at the effectiveness of bone marrow aspirate (BMAC) for the treatment of osteoarthritis. A recent review identified six trials for osteoarthritis and cartilage defects. It reported that only modest improvement was found and that a placebo effect could not be ruled out with stem cell injections. In another example, researchers from the Mayo Clinic reported on twenty-five patients who had bilateral knee osteoarthritis. BMAC was injected in one knee, and saline (a harmless fluid and salt solution) in the other knee. They reported no difference in symptoms at six months or one-year postinjection between the groups.

Reported side effects for bone marrow aspirate procedure include self-limited pain and swelling. For culture-expanded stem cells, the most concerning adverse effect is that these cells can develop into unwanted tumoral cells. Furthermore, manipulation in the laboratory has risks of contamination of the cells.

Should I use stem cell injections to prevent getting osteoarthritis?

There is no evidence to support stem cells being used as a preventative treatment for knee arthritis. Current literature on the use of stem cells only provides evidence for diseased joints. Given the fact that no therapy is without risks, it is not recommended that these therapies be used for prevention of joint degenerative disease.

Should I participate in a clinical trial on stem cell treatment?

Because of the relatively safe profile reported in previous studies, enrolling in a clinical trial could be a good option for you if you fit the inclusion and exclusion criteria for the study. All clinical trials have been screened by an institutional review board that protects patient rights and maximizes patient safety. Carefully read the informed consent form for potential advantages and complications, and make sure you ask all the questions you need answered before enrolling. Of note, you can leave the study at any point without any penalties.

We believe biological therapies will be increasingly used in the future not only in sports medicine and orthopedics but in medicine in general. Further clinical trials with long-term follow-up will help doctors determine how and when to use these therapies and if they are truly safe for patients suffering from arthritis. Several laboratories in the United States, including ours at the Steadman Clinic and the Steadman Philippon Research Institute, are working on biological replacements of joints (trying to regenerate cartilage, instead of using metals) after end-stage osteoarthritis, which could become the gold standard in the future.

The science on these treatments is constantly evolving. Significant changes for the most debated use of stem cells should be expected to occur in five to fifteen years. Their approval and widespread use could be accelerated.

How Much Do Injections Cost?

Prices vary by geographic region, as well as by the clinic performing the procedure. Steroid injections and hyaluronic acid injections for arthritis are almost always covered by insurance. If cortisone or gel injections are not covered by insurance, they can cost between $150 to $300 and $300 to $1,500, respectively. PRP injections cost approximately $1,500. The cost of bone marrow aspirate stem cell procedures varies from $2,000 to $5,000.