Now that we have the basic science under our belts, we can turn back to the concept of regenerative medicine…

Platelet-rich plasma (PRP)

Platelet-rich plasma (PRP) is the product of using specialized centrifuge techniques (putting the test tubes in a spinning machine) to separate platelets from whole blood (separate the blood into its different components). Platelet-rich plasma (PRP) is a suspension of concentrated platelets in a small volume of plasma (as discussed above; the liquid portion of blood). The whole process takes approximately 15 minutes and produces a platelet concentration of 3–5x that of regular blood.

Platelet-rich plasma (PRP) has been advocated as “regenerative” medical treatment. It is proposed PRP boosts are own body’s natural tissue healing and regeneration capabilities through the local introduction of increased levels (above baseline) of platelets and their associated bioactive molecules (specifically the growth factors mentioned in the inflammatory phase of wound healing, above). In theory, the increased levels of autologous (from your own body) growth factors (GFs) and other proteins provided by the concentrated platelets may enhance the wound healing process.

Researchers believe the primary benefit of PRP is platelets are a natural source of growth factors (GFs). Growth factors, stored within platelet α-granules, include platelet derived growth factor (PDGF), insulin like growth factor (IGF), vascular endothelial growth factor (VEGF), platelet derived angiogenic factor (PDAF), and transforming growth factor beta (TGF-β). We have learned, these growth factors help with the following components of healing:

  1. GFs help recruit reparative cells to the site of injury
  2. GFs help increase growth of little blood vessels involved in the early wound repair process (angiogenesis).
  3. GFs promote cell proliferation (replication and division of cells, or “growth),

What Conditions are Treated with PRP?

The concept of PRP is not new; autologous platelet-rich plasma has been used over the past 3 decades in dentistry, ophthalmology, maxillofacial surgery, and cosmetic surgery. Research into the efficacy of PRP for musculoskeletal disorders is ongoing. Treating tendons, ligaments and cartilage injuries with PRP is not without controversy. Even though the basic science data supporting the potential beneficial effects of growth factors (key component of PRP) in augmenting connective tissue healing is promising, the clinical benefits of using PRP to improve functional outcomes have been inconsistent.

Currently, common conditions treated with PRP injections (and, of course, supportive rehabilitation) include:

  1. Tendons:
    • Tennis elbow (lateral epicondylopathy)
    • Achilles tendinopathy
    • Patellar tendinopathy (between the kneecap and the top of the shin bone)
    • Gluteus medius tendinopathy (tendon from the outer glute muscle that attaches to the greater trochanteric and may or may not be associated with bursitis)
  2. Ligaments:
    • Medial collateral ligament (MCL) sprains of the knee
    • Acromioclavicular joint sprains (A-C joint) of the shoulder
  3. Joints/Cartilage:
    • Early knee osteoarthritis (OA),
    • Early hip osteoarthritis (OA).

One potential reason for the lack of translation from the lab (in vitro studies are very encouraging) to clinical results (clinical studies have had mixed results) is the wide variance in the final PRP product.

The large variance of the PRP preparations currently offered to patients (both for clinical studies and everyday use) is causing confusion to the medical community (interpretation of research results) and the patient population (does PRP work? Where should I go for my treatment?). Therefore, it is incumbent upon anyone using a specific PRP product to understand the product they are offering. In addition, it is the responsibility of the patient to pursue basic knowledge of the medical treatment they are pursuing, so they make informed decisions.

Stem Cell Therapy

Stem cells are unspecialized cells (undifferentiated) of the human body. They are able to differentiate into any cell of an organism and have the ability of self-renewal. Stem cells exist both in embryos and adult cells. Stem cells provide new cells for the body as it grows and replace specialized cells that are damaged or lost.

Stem cells, therefore, act as the internal repair systems of the body. Although stem cells appear to be an ideal solution for medicine, there are still many obstacles that need to be overcome to fully understand the safety and efficacy of stem cell therapy.

Types of stem cells: Understanding stem cell potency: It is common to divide stem cells into two categories:

  • Embryonic stem cells (ESC). These stem cells come from embryos (fertilized egg) that are less than five days old. These are pluripotent stem cells, meaning they can differentiate (specialize) into any type of cell in the body.
  • Adult stem cells. These stem cells are found in adult tissues, such as bone marrow or fat. Adult stem cells have a more limited ability to give rise to various cells of the body. The disadvantage of adult stem cells is the difficulty in harvesting the number and quality of cells necessary to successfully treat the target condition. The advantage of the adult stem cells is in their predictability; there is a much lower probability adult stem cells will develop into an unexpected type of tissue (remains controversial).

Scientific (more detailed) discussion of types of stem cells and their potency:  The following discussion may be difficult for an individual without a science background to absorb. But, this is useful information in the pursuit of a decent understanding of stem cell science.

As stem cells differentiate and become more mature, their developmental potency is reduced. The following is a brief explanation of the sub-types of stem cells that exist in humans, beginning with conception (getting pregnant):

1. Totipotent stem cells. The best example of a totipotent cell is a zygote, which is formed after a sperm fertilizes an egg. When an egg is fertilized by sperm in the fallopian tube (just outside the uterus) it becomes a zygote. The zygote is a single cell that contains all 46 of the chromosomes (DNA) needed to become a fully developed human. A zygote is pretty much the first stage of human life. Totipotent cells are able to divide and differentiate into cells of the whole organism. Totipotency has the highest differentiation potential (ability to sub-specialize into different types of cells) and allows cells to form both embryo and extra-embryonic structures. This type of stem cell is not commonly discussed in context of treating common musculoskeletal injuries. {totipotent cells are mentioned to avoid voids in the basic science education}

2. Pluripotent stem cells (PSCs) are almost as “powerful” as totipotent stem cells. PSCs can also form cells of all germ layers (all types of human tissue), with the exception of the placenta.

Embryonic stem cells (ESCs) are an example. Reminder to science students: The zygote undergoes some evolution (cell division) in the first few days the zygote will become an embryo, then a morula, then a blastocyst. When the embryo grows to the level of blastocyst, it is ready for implantation in the uterus. ESCs are derived from the inner cell mass of preimplantation embryos (blastocyst).

Another example is induced pluripotent stem cells (iPSCs) derived from the epiblast layer of implanted embryos. iPSCs are artificially generated (an individual’s cells are modified in a lab) similarly to PSCs. iPSCs are promising for the future regenerative medicine, but are not currently the standard of care.

3. Multipotent stem cells have a narrower range of differentiation (ability to specialize) than PSCs, but they still have significant capacity. They can specialize into cells of specific cell lineages (cells of one germ layer). For example, a multipotent blood stem cell can differentiate itself into several types of blood cells; red blood cells (RBCs) and different types of white blood cells (WBCs).

Most stem cells used for the experimental treatment of osteoarthritis are adult mesenchymal stem cells (MSCs). These cells are typically collected from fat or bone marrow. MSCs are multipotent, capable of specializing into cartilage, bone, muscle, tendon, ligaments, or fat. Which tissue they differentiate into depends upon their environment (type of tissue cells are inserted into).

The influence of MSCs on joint disease (e.g. osteoarthritis) is not fully understood. Beyond the hope of tissue regeneration, there are other potentially beneficial effects. The injection of MSCs can be associated with the release anti-inflammatory factors. Some believe the benefits of MSCs relates to the enhancement of the wound healing cascade, similar to PRP.

4. Oligopotent stem cells can differentiate into sub-types of particular lineage. Using the same example of blood cells; a lymphoid cell can give rise to various blood cells such as B and T cells, however, not to a different blood cell type like a red blood cell

5. Unipotent stem cells are characterized by the narrowest differentiation capabilities and a special property of dividing repeatedly. Their latter feature makes them a promising candidate for therapeutic use in regenerative medicine. These cells are only able to form one cell type. So, their use can be focused.

Stem Cell Therapy for Osteoarthritis (OA).

Most injection-based treatments use a patient’s own MSCs (called autologous MSCs) taken from their bone marrow or fat. The odds of this type of intervention resulting in the stem cells developing into an unintended tissue type, is extremely low.

Despite the fact research to date shows that stem cell treatments using a patient’s own cells tend to be safe for OA, the Health Canada has not approved stem cell therapy at this time.

Critics of stem cell intervention emphasize that there have been no large-scale, prospective, double-blind research studies to support stem cell therapy for arthritis. Critics are also concerned that the assumption that adult stem cells are safe and will develop into the target issue without incident is a premature conclusion.

It is likely, in the near future, enough support for the safety and efficacy of stem cell treatment in well selected osteoarthritis patients will be published to restart this type of care for Canadian patients. In the short term, stem cell intervention is not available in Canada.