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PRP and Stem Cells

Many active athletes, weekend warriors, and folks with arthritic joints have been asking about two treatment options for their pain: Platelet Rich Plasma (PRP) and “Stem Cells.”  Both treatments have become increasingly popular, but at the same time, there is a lot of false information about them, especially online.  For this reason, I think it’s important that I update my patients.  These procedures are also not covered by insurance, so we want our patients, who are eligible, to be well informed before undergoing such treatments.

The focus of this information is on joint cartilage injuries, arthritis and focal cartilage defects (potholes in cartilage).

PRP and Stem Cells

PRP comes from your own blood. Platelets are naturally found in your blood and help with clotting after an injury. They also have growth factors that can induce new blood vessel growth to help in recruiting other healing cells to an injured area. 

Why isn’t PRP always effective?

First we draw blood and then it is ‘spun’ in a centrifuge to separate out the platelet layer, which is then removed. Many different companies provide systems to do this; however, not all PRP is the same.  The various systems that are engineered to harvest PRP also are able to harvest other cells.  Additionally, the concentration of platelets per unit volume differs among systems.  With that said, initial clinical studies on “PRP” have had mixed results because different systems produce different types of PRP. 

For example, some PRP formulations contain a high number of leukocytes (white blood cells).  These formulations are called Leukocyte Rich PRP (LR-PRP).  Depending on the formulation of PRP and condition we’re treating, some patients may experience a positive response and some patients may actually feel MORE pain. It’s important to discuss which formulation is best for you.

These cells have a pro-inflammatory response when exposed to tissue.  When they’re injected in degenerative tendons that cause pain, (hamstring, Achilles, patellar, tennis elbow) they can have a positive effect because it creates an inflammatory response that aids in healing.  But, if a PRP mixture that contains high leukocytes is injected into a knee to treat osteoarthritis pain, it can actually worsen the pain by increasing inflammation in the knee.  Here’s when PRP is helpful: When a leukocyte poor (low number of white blood cells) mixture of PRP (LP-PRP) is injected into an arthritic knee, it has been shown to be better than other injectable medicines (hyaluronic acid, e.g. Synvisc, Euflexxa, etc.) at relieving pain. 

What you need to know about stem cells first:

Just as PRP can vary in its content, not all stem cells are created equal.

Stem cells can either come from you or someone else.  If they come from someone else, they are called allogenic, and are usually from amniotic stem cells.  If they come from you, they are called autogenic and come adipose (fat) derived stem cells or bone marrow derived stem cells.  One of the easiest ways to get your own stem cells is when they’re retrieved from your pelvic bone.  This is called bone marrow aspiration.  These cells can then be separated out from the blood and injected as Bone Marrow Aspirate Concentrate (BMAC).  This is the most popular way to harvest stem cells in this country.  One challenge of this method is not being able to retrieve a high enough concentrate of stem cells to be effective for treatment. The problem with this technique is it yields stem cell numbers in the thousands per milliliter.  If we extrapolate from the veterinary literature regarding stem cells (mostly horses, sheep, and dog studies), we know that in order to obtain true cartilage regeneration, we need stem cell concentrations on the order of 1 million per milliliter at a minimum.  This is difficult to obtain and usually occurs by culturing (growing the number of) these cells in a lab and then subsequently re-implanting them as part of a second procedure.  Of note, interestingly, the number of stem cells per milliliter that can be harvested from fat is markedly higher than bone marrow.  This makes fat an ideal place to get them, but we are limited by the FDA on where we can inject these cells. 

In the United States, stem cell therapies are a controversial topic on a national level.  The FDA has strict laws regarding their use because of concerns surrounding genetic manipulation and using embryonic stem cells for research purposes.  Two key terms are important: homologous use and minimal manipulation.  Homologous use means you cannot take stem cells from one part of the body and use them in another part.  You can’t transfer cells away from their origin.  Minimal manipulation means that you can’t significantly change them. (An exception: cancer specialists have been using bone marrow transplants for years for cancer patients, so bone marrow aspirate has been “grandfathered in.”)

Doctors can use bone marrow aspirate cells for any purpose around the body, but adipose (fat)  derived stem cells cannot.  As an example, one cannot harvest fat from the belly, extract the stem cells from that mixture, and inject it into the knee.  This is considered non-homologous use by the FDA.  You can however, obtain fat from the small fat pad that everyone has behind their patellar tendon (inside the knee joint), extract those cells, and then inject them into the knee.  The problem is that there is only a small volume of fat in this area, and thus a limited number of stem cells.  It is important to point out that there are companies/physicians that will inject adipose derived stem cells into other parts of the body, but this is a controversial topic with regard to current FDA compliance standards.  There is a new push by the FDA to regulate these businesses.

So, why can’t these wonderful elements work for cartilage repair in joints?

Each human joint is a very specialized structure.  Cartilage is the white tissue that caps the end of the bone and protects it.  The coefficient of friction of cartilage rubbing on cartilage is slicker than ice on ice, yet it has to withstand the shear and compression forces of weight bearing every day.  Cartilage is a high priced commodity because when it’s damaged, it’s pretty hard to completely repair or regrow it because of its lack of blood supply and regenerative cells.

So the million-dollar question is this: How do we consistently re-grow cartilage once it has worn down?  This is where stem cells come in to play.  Despite what you may see in the media, we currently, do not have a reliable way to re-grow cartilage from a stem cell injection in the U.S.  We don’t know how to get the cells to stick to the correct spot in the joint (especially in an environment where joint fluid is present and motion that is nearly constant), turn on to form cartilage, and provide a protective barrier for the bone.  Research is ongoing in this field and there are promising, early results, especially in Europe.

Recently, I heard Jason Dragoo, MD from Stanford give a wonderful review presentation on this very topic at the American Orthopaedic Society for Sports Medicine Annual Meeting.  Most of the data below is taken from his summary of the current scientific and clinical literature surrounding PRP and stem cells. 

Here’s what the literature says about PRP and Stem Cells (SC) to treat focal potholes in cartilage (Isolated Cartilage Defect) and arthritis (general rough road and wear/tear of the cartilage).  It comes from basic science data (testing in labs) and real patient trials.

PRP and Cartilage Defects:

Basic science shows some promising results with PRP for cartilage regeneration compared with other injectable treatment options.  However, in clinical trials, there is no solid evidence that it works with just (one?) injection(s?).  When PRP is used in combination with other surgical procedures (Microfracture) it has promising results with improved cartilage growth compared with Microfracture alone.  The general recommendation is that injectable PRP should not be a first line treatment option for a focal cartilage defect.

PRP for Arthritis

The data is much more promising for PRP in treating arthritis.  PRP injections are considered
“experimental and investigational” by all insurance companies and Medicare.  This is because the clinical trial data is mixed on its ability to help pain or re-grow cartilage.  However, as we said above, PRP comes in different formulations.  The ability to extract PRP with high vs low white blood cells in the mixture can alter its ability to control pain in the setting of arthritis.  From a basic science standpoint, low white blood cell PRP (LP-PRP) may be useful for joint preservation because it has an anti-inflammatory effect to calm down the products in the knee that destroy cartilage.  PRP that has a high number of WBC (LR-PRP) has a pro-inflammatory effect that may be very useful in chronic tendon problems (patellar or hamstring tendon), but it increases the inflammation in a joint with arthritis and does not provide pain relief. 

The PRP trials that are the best type of data (randomized controlled trials) looking at arthritis symptoms and the effect of PRP on these symptoms show mixed results.  All of these trials compare PRP to hyaluronic acid (Synvisc, as an example—commonly referred to as the rooster comb injection).  Of the trials that show a positive effect on pain improvement compared with hyaluronic acid, five are LP-PRP and one is LR-PRP.  Of the trials that show a negative effect (no pain improvement), none are LP-PRP and three are LR-PRP. 

In summary, LP-PRP improves the symptoms of inflammation and arthritis.  These results are improved over hyaluronic acid injections.  LR-PRP should not be used for arthritis treatment.

Stem Cells for Focal Cartilage Potholes and Diffuse Osteoarthritis

There are multiple studies using animal models (pig, sheep, dog, and rabbit) to evaluate the use of mesenchymal stem cells to treat focal cartilage defects.  Nearly all of them found some improvement (often significant improvement) in cartilage regrowth.  However, these stem cells are often embryonic or derived from a source (placenta) that we cannot use in the United States.

Clinical trials are limited in this country.  The existing studies compare existing treatment options for cartilage defects [Microfracture, autologous chondrocyte implantation (ACI)] to those treatments and add stem cells to them.  The results are essentially the same.  There is currently a multi-center human randomized clinical trial comparing Microfracture to arthroscopically obtained (from the fat pad in the knee) fat derived stem cells with no Microfracture.  Results are likely several years away.

Stem Cells for Arthritis:

The best data about stem cells for arthritis comes from Asia.  There are multiple studies that show injection of stem cells into an arthritic knee may induce new cartilage formation.  These results were verified by surgical arthroscopy (with a camera) to look at the cartilage.  Some caveats with the study: It took 100,000,000 fat derived stem cells in one injection to obtain these results and the number of patients treated was small (12).  We don’t have the ability to obtain this amount of fat derived stem cells in this country through simply harvesting from the fat pad in the knee. 

The Bottom Line?

In summary, bone marrow derived and fat derived stem cells can be used to treat cartilage defects and arthritis due to an overwhelming amount of evidence of efficacy in animal models.  However, human trials are lacking. 

The field of orthopaedic biologics continues to evolve.  We will update you as new, impactful research becomes available.