Biologic Therapy
The body has an innate ability to heal itself.
Researchers have long attempted to understand the body’s healing processes and use them in the treatment of injury and degeneration. Part of the body’s adaptive responses to injury comes from cellular components and factors—such as platelets and certain types of cells—and substances made by or contained within them. The effects exerted by these cellular factors assist in tissue restoration and regeneration in a healthy body.
Treatments using platelet rich plasma (PRP) and mesenchymal signaling cells (MSC) are considered biologic therapy (also called orthobiologics therapy). In these treatments, cellular components and factors are harvested from the patient’s own body, processed appropriately, and used to treat a variety of orthopedic, musculoskeletal, and neuromuscular conditions. These bioactive substances are derived and injected into the area of damaged or degenerative tissue—an injured muscle, an inflamed tendon or an arthritic joint, for instance. The current understanding and rationale are that these cellular substances may:
- Contribute to reparative processes in the body via signaling and/or communications between cells.
- Help create an environment conducive to tissue healing, through modulating inflammation and stimulating local cells and bioactive proteins.
The objective of biologic therapy is to improve the healing and local environment of injured tissues – be it muscles, tendons, ligaments, cartilage, joints, fascial, or nerves. It is also currently being used to address the pain and inflammation that accompany degenerative conditions, such as arthritis. For those with arthritis or damage to the articular cartilage who don’t feel ready for knee replacement, the aims of these treatments include serving as a “bridge” between cartilage repair procedures and total knee replacement.
At this time, orthobiologic therapies are considered “symptom-altering.” The extent to which these substances are “structure-altering” is still unclear.
How Does It Work?
How do orthobiologic injections improve healing? This question is still being answered accurately, but we do know that these treatments work through a complex series of interactions. The healing process from injury requires multiple steps, and often begins with fighting and protecting against infection, which involves a “break-down” type of inflammation. As the injury responses progress, they transition to a “build-up” type of inflammation. However, before tissue regeneration and remodeling can begin in earnest, the “break-down” inflammation needs to be controlled. And this occurs through the mobilization of many cells and mediators, which modulate inflammation, and help initiate tissue regeneration. Platelets, certain white blood cells, and MSCs all play important parts of this healing cascade. And it is
these processes, functions, and cellular components that orthobiologics (biologic therapy) seeks to use in addressing the clinical concerns of patients.
PRP is comprised of platelets, white blood cells, and heavier plasma proteins and has very effective growth factors and cytokines. These are expressed by the platelets and exert their effects once injected into a target tissue area and activated from inside the patient’s body.
Currently, when harvested, processed, and injected into a patient in an FDA-compliant manner, MSCs act as medicinal signaling cells, or tiny pharmacies, to bring in proteins and cell factors that stimulate and modulate the body’s own repair mechanisms to work more effectively in areas of injury, degeneration, or inflammation. These are most easily accessed in the bone marrow and fat:
- Bone marrow-derived (bone marrow aspirate concentrate; BMAC)
- Fat-derived (micro-fragmented adipose tissue; MFAT)
What is PRP?
Platelet-rich plasma (PRP) is derived from your blood. Platelets are small cell fragments in your blood that contain an abundance of growth factors and anti-inflammatory agents important for tissue healing. These include IGF, TGF, VEGF, and many others.
When an injury occurs, the body delivers platelets to the injury site, which release bioactive factors that help stop bleeding and stimulate the initial steps for tissue repair. This is the natural process by which nearly all tissue heals. For PRP therapy, a sample of your blood is obtained, the platelets are concentrated and isolated, and then injected into the desired body part.
What are MSCs?
“Mesenchymal Stem Cells” include progenitor cells and pericytes (those that line blood vessels) and have the potential to transform into other tissue types. A “stem cell” has a specific definition as to its biologic potential and other criteria under ideal laboratory conditions. Under these conditions, these “stem cells” have the ability to transform into varying cell types and tissues – and populate areas of damage, facilitating healing and regeneration of new tissues, under experimental conditions – whether that be skin, heart, tendon, cartilage, or bone. The type of “stem cell” most relevant to orthopaedic conditions is the “Mesenchymal Stem Cell.” However, the FDA frowns upon the use of this term for the clinical treatment of human patients. One rationale for avoiding the term “stem cells” here is that these cells would not be acting under ideal conditions inside of a patient, and therefore cannot be expected to act as a “stem cell” that transforms and grows into new tissue. Instead, they are expected to have other effects within the patient, that control inflammation and break-down processes, as well as stimulate and support tissue repair, in general. For this reason, the preferred terms for these cells include:
- Mesenchymal Signaling Cells (MSCs)
- Medicinal Signaling Cells
The Procedure
PRP: the procedure
Platelets are harvested from your blood. This is an office procedure that may take as little as 20-30 minutes. Some cases may take longer. A sample of blood is drawn from one of your veins, typically from your arm. The blood sample is processed, usually by centrifugation, and a part of the plasma layer of blood – which is rich in platelets – is isolated, removed and injected into your affected joint or injured area.
Your activities after the procedure may be limited according to the treated condition and should be discussed with your physician.
MSCs: the procedure
MSC injections can be performed in the office or procedure center. Bone marrow (BMAC) and fat (MFAT) are obtained through a minor procedure that may take 30-60 minutes.
MSCs from bone marrow (BMAC) may be derived from the crest of your pelvic bone (the ilium). The area is anesthetized, and a needle is placed into the marrow cavity. A marrow aspirate is withdrawn, processed, and concentrated – usually by centrifugation, using techniques that satisfy the FDA requirements for “no more than minimal manipulation” and have been shown to isolated MSCs. The resulting BMAC is then injected into the affected joint or injured area.
MSCs from fat (MFAT) may be harvested from the fatty tissue in your belly or flank. The area is anesthetized, and a needle is placed into the fatty layer under the skin. Adipose tissue is then withdrawn and processed, using techniques that satisfy the FDA requirements for “no more than minimal manipulation” and have been shown to isolated MSCs. The resulting MFAT is then injected into the affected joint or injured area.
Your activities after the procedure may be limited according to the treated condition and should be discussed with your physician.
Frequently Asked Questions
Which are better: PRP or MSCs?
We don’t have the answer to this. Research has shown that both procedures are considered effective to enhance tissue healing and joint pain control. The research is constantly evolving, and there may be specific considerations relevant to your individual case and should be discussed with your physician.
How many injections are required?
This is a subject of ongoing study. Most MSC studies report on a single injection. PRP studies report on both single and series of several injections separated by weeks or months, though the evidence has not demonstrated that multiple injections are clearly superior to a single injection. There may be specific considerations relevant to your individual case and should be discussed with your physician.
If I have an MSC injection into my arthritic knee, will it grow new cartilage?
Some studies have shown MSCs being able to engraft and grow new tissue after being injected into a human subject. However, these have all been done using techniques of culture expansion and “more than minimal manipulation” that are currently forbidden by the FDA, government regulations, and other legal entities in the United States (US). Studies on MSC harvesting and preparation techniques that are allowed by current FDA regulations have shown that MSCs derived from these FDA-compliant techniques do not engraft and grow into new tissue. However, the injected MSCs do have a positive effect on the local tissue environment, making it more conducive to cell growth and regeneration. So, MSCs done legally in the US are thought to be more of a pain or inflammation control mechanism than a tissue replacement and regrowth mechanism, i.e., “symptom-altering” rather than “structure- altering.” One may achieve significant pain control for a moderate period of time, possibly years. However, it is very unlikely that an orthobiologic injection will reestablish a new layer of cartilage in a meaningful way.
I’ve heard about amniotic membrane products, and other “stem cell” treatments – what about these?
Recently, several other products – including amniotic products, exosomes, umbilical cord blood, and Warton’s jelly – have been disallowed or forbidden by the FDA. Caution is advised when considering these products, currently, and we advise that you discuss any questions or concerns you may have with your physician.
How long will the effect of an orthobiologic injection last?
This is variable according to the degree of tissue or joint damage, as well as your own biology. Studies have shown that the pain-controlling effects of orthobiologic treatment may last up to several years. We do not, however, consider these injections to be curative by themselves, and it may be important to consider them as part of a larger comprehensive treatment strategy. There may be specific considerations relevant to your individual case and should be discussed with your physician.
How fast do these injections work?
This is variable according to the degree of tissue or joint damage, as well as your own biology. Although the cells may well go to work immediately, the effects may take some time to be appreciated. The effects of an injection in an acutely injured muscle may be noticed within a few days. However, many clinicians believe that a degenerative joint may take two months before one can expect to notice clinical improvement. There may be specific considerations relevant to your individual case and should be discussed with your physician.
Which MSC preparation is preferable – BMAC or MFAT?
This is the subject of much investigation and debate and is yet to be fully answered. Each product contains a mixture of cells and bioactive proteins, or cytokines, that effect a tissue response. What the combination of cells and proteins is varies according to the harvesting and preparation techniques, as well as the patient biology. We have yet to fully understand which cells and proteins are most important. These questions and many others are the subject of ongoing investigation.
What does the research show?
Orthobiologics is a hot-button topic in medicine these days. Biologic products and techniques are being used in orthopedic, musculoskeletal, and neuromuscular medicine with regularity, despite the fact that we do not fully understand their definition or efficacy. Reports in the literature vary. Many studies show improvement in pain and function. Other studies report equivalent outcomes of orthobiologics to a placebo. It could be years before we have all the answers. Additionally, each patient is unique, and each case is different – we advise that you discuss any questions or concerns you may have with your physician.
Are orthobiologic injections covered by insurance and how much does it cost?
At the present time, most insurance policies do not cover orthobiologic injections. They are considered investigational and “off-label use” (your physician can explain this to you in detail). Speak to your physician’s office regarding the price profile, which varies according to the product and procedure used. Consult your health savings account advisor to see if these qualify.
Do I make an appointment for a PRP or MSC injection?
A screening appointment and consultation is necessary to first determine if you are a candidate for an orthobiologic injection. This may involve x-rays and possibly an MRI. Then, you and your health care can determine if biologic therapy is appropriate for you. A separate appointment for the procedure is then arranged.
This page is intended for educational purposes and does not address individual patient needs. Please consult your physician to determine the treatment option that is right for you.