06/02/2021
One Physician’s View of PRP and other Regenerative Medicine Products
Platelet Rich Plasma
Platelet Rich Plasma (PRP) has been a mainstay of nonsurgical orthopedics for twenty years. There is currently Level II research (evidence obtained from at least one well controlled RCT [randomized controlled trial]) supporting its use in many orthopedic conditions (e.g., knee osteoarthritis, hip osteoarthritis, rotator cuff tendinitis, and partial tearing of the rotator cuff to name only a few). When compared to cortisone for osteoarthritis and tendinitis in double blind controlled trials, it beats cortisone hands down when measures of pain, function, longevity of effect, and disability are used. It is also being used for sexual health (e.g. Priapus shots (O-Shots) and urinary incontinence), hair restoration, aesthetics, certain types dental procedures, certain types of neurosurgery and certain types of plastic surgery to expedite healing. In short, PRP is well established in multiple areas of medicine however, that is not the end of the story.
Plasma Rich Platelets (PRP) is derived from the patient’s whole blood. The process involves aspirating a variable amount of blood, separating the patient’s red blood cells from the blood and concentrating the platelets in the patient’s plasma … thus the name Platelet Rich Plasma.
The concentration of platelets in a healthy individuals’ whole blood ranges between 150,000 – 450,000/cc. An average platelet count in a typical healthy adult is ~250,000/cc. A PRP specimen must have >1,000,000 platelets/cc to be considered “PRP”. However, not all PRP is created equal. There are many different manufacturers of PRP kits which have different capacities to concentrate the platelets and different capacities to separate red blood cells from plasma. As a general rule, red blood cells in soft tissues or joints create inflammation and may cause increased pain, swelling, and scarring at the injection site so it is considered important to thoroughly remove the red blood cells from the PRP specimen*. Moreover, the effectiveness of the PRP specimen varies with age and health of the individual patient. Recent data evaluated the growth factor (GF) and interleukin (IL) concentration of twelve healthy individuals, four 21 year olds, four 37 year olds, and four 61 year olds. Growth factors stimulate cell proliferation, wound healing, and cellular differentiation. Interleukins are small proteins that regulate the immune and inflammatory response to cell signaling molecules (e.g., cytokines). Not surprisingly, the GF and IL concentrations plummeted with age. Growth factor and IL concentrations are also impacted by conditions like diabetes and overall health of the individual. These are only some of the considerations surrounding PRP and are only some of the reasons that results from PRP therapy are not the same for varying ages and stages of health.
It is clear in the research that for knee osteoarthritis (for example) that the outcome of PRP therapy is much better for early osteoarthrtitis (OA) than late or advanced stages of OA. Kellgren and Lawrence developed the Kellgren-Lawrence Scale (KL scale) for OA which has proven to be very useful. The KL scale divides knee OA into four categories based upon the degree of narrowing (loss of cartilage height) in standing knee radiographs. KL scale 0 = no OA, KL scale 1 = mild OA, KL scale 2 = mild-moderate OA, KL scale 3 = moderate OA, and KL scale 4 = severe OA (i.e., bone on bone). The results of PRP are much better for KL scale 1-3 as opposed to KL scale 4.
In summary, my experience demonstrates that PRP therapy has merit but mostly for healthy young or middle-aged individuals. With advanced age, advanced degenerative condition, or failing health, there are probably better ways to achieve the same goal of pain relief and/or improved function (orthopedic issues), improved hair growth, improved sexual function, or improved skin integrity (aesthetics).
Mesenchymal Stem Cells
In the United States, the entire area of regenerative medicine is under review by the FDA. Stem cells and related products are particularly under scrutiny. As of the time of this writing, the FDA considers anything other than minimally manipulated autologous tissue a drug and thus is treating/investigating it as such. The type of stem cells of most interest to regenerative medicine are mesenchymal stem cells**. In addition, the FDA has indicated that minimally manipulated bone marrow derive stem cells (Bone Marrow Autologous Concentrate, BMAC) may be appropriate to inject into the patient’s joints and tendons and that minimally manipulated stem cells derived from fat are appropriate to inject into a patient’s face or other body parts. The sentiment of the FDA is that it may be reasonable to use autologous tissues in a therapeutic fashion if it is in a way that the body would use them under normal circumstances.
It is well established that bone marrow-derives stem cells (MSC’s) plummet in concentration with advancing age. Many researcher have found that beyond age 50, not only has the number of MSC’s declined (~50% of MSC concentration in people in their twenties) but the ability of the MSC to divide and effect positive change in the body also significantly declines. Yes, there are methods of concentrating stem cells to offset the reduction in concentration of MSC’s with advancing age but this does not improve the capacity of older MSC’s to perform their desired function.
The concentrations of MSC’s in fat remains relatively constant from age twenty to age eighty. Fat may be harvested and then put through a minimal manipulation known and micro-fractionated fat autologous transfer (MFAT) and used for regenerative medicine purposes. However, as with BMAC, the “fitness” of the MSC declines with the age and health of the individual. Studies demonstrate an increase in cellular senescence, reduced capacity for cell division, and reduced capacity to effect positive change. Proponents of MFAT use this therapy to help repair damaged joints, tendons, and soft tissues. MFAT is also being used for aesthetic purposes such as fat transfers to the face, hands, breasts, and gluteal region.
Other Regenerative Products in the United States
The area of Regenerative Medicine is rapidly evolving . Earlier forms of regenerative medicine include prolotherapy. Prolotherapy uses dextrose and other products to cause inflammation and stimulate the body’s own healing response. In the past this was used to promote healing of torn ligaments of the spine and joints. It is still being used by some practitioners today.
Many practitioners believe that medical ozone has merit. Ozone is the same gas as in our stratosphere. It is O3, an unstable form of oxygen with a half-life of ~20 minutes at a temperature of 21 degrees Celsius (69.8 degrees Fahrenheit) and one bar of atmospheric pressure (0.987 Atmospheres). The gas is highly anti-inflammatory, antimicrobial, stimulates wound healing, and stimulates the immune system among other positive effects. Ozone has been evaluated for medical purposes for over 100 years however RCT’s (randomized controlled trials) are still lacking.
There are several other regenerative medicine biological products available that may have great merit in certain clinical conditions. Current research is using an outcome-based approach to many of these biological products. As mentioned above, GF’s and IL’s are naturally occurring molecules in the body. Growth factors stimulate cell proliferation, wound healing, and cellular differentiation. Interleukins are small proteins that regulate the immune and inflammatory response to cell signaling molecules (e.g., cytokines). It is largely known which GF’s and IL’s are beneficial for wound healing, musculoskeletal injury, neurodegenerative conditions, and autoimmune conditions. These biological allografts (tissue derived from a donor of the same species) are being derived from donated and tested placental products that are focused on specific conditions (e.g., musculoskeletal recovery, osteoarthritis, etc.) and have a far higher GF and IL concentration than a young person’s PRP and thus should yield improved results, particularly in those of advanced age and/or poor health.
These products are not FDA approved and are still being evaluated and an individual considering their use should discuss the FDA approval status with their Regenerative Medicine care provider.
Robert Windsor, M.D.
* Some research suggests that it is advantageous to leave some red blood cells in the PRP specimen when injecting a tendon or ligament.
** Mesenchymal stem cells (MSC’s) primarily create and modify bone, cartilage, muscle and connective tissue.
