Regenerative medicine is the field of study which involves the process of replacing or “regenerating” human cells, tissues or organs to restore or establish normal function. This field holds the promise of repairing damaged tissues and organs in the body.

What regenerative medicine treatments are available for musculoskeletal injuries (joints, tendon, ligament)?

The most commonly discussed regenerative therapies for musculoskeletal injuries are:

  • Stem cell therapy
  • Platelet rich plasma (PRP)

Stem cell therapy and platelet rich plasma are not the same. However, there is overlap with how these two treatments influence the body’s efforts to repair musculoskeletal injuries.

  • PRP primarily works to boost the body’s natural healing mechanisms.
  • Stem cells, theoretically, have the ability to “regenerate” tissue. Realistically, when discussing the current available stem cell treatments for musculoskeletal injury, stem cells carry out their primary effect by enhancing our natural healing mechanisms (similar to PRP). In medicine, we refer to this repair process as wound healing.
  • “Regeneration” of new tissue with stem cell technology is likely within our grasp. In fact, in animal studies, regeneration of soft tissues has been demonstrated. However, it is not clear that the benefits we are seeing in real life (injured humans) are related to “regeneration” in the strictest definition of the term. More likely than not, stem cell treatments with autologous stem cells (harvested from your own body) exert their influence by enhancing our natural healing mechanisms.
  • Because the assumed benefits of both PRP and stem cells are understood to relate to enhancement of our natural healing processes, it makes sense to discuss the basic science of wound healing to improve our understanding of this type of medicine…

Wound Healing

Wound healing is a dynamic physiological process for restoring the normal architecture and functionality of damaged tissue. A highly detailed discussion of the steps involved in wound healing is beyond the goals of this website. However, a grasp of the basic science may be useful to the patient, therapist or family physician to improve communication surrounding treatment options. To comprehend wound healing, one must have a basic understanding of the components of our blood.

In other words…

  • One needs to know the basic science of blood components to understand wound healing.
  • One needs to know the basic science of wound healing to understand the current state of regenerative medicine.

Understanding the components of blood

  1. Plasma: The blood that runs through our veins, arteries, and capillaries is known as whole blood, a mixture of about 55 percent plasma and 45 percent blood cells. The liquid component of blood is called plasma, a mixture of water, sugar, fat, protein, and salts. The main job of the plasma is to transport blood cells throughout your body along with nutrients, waste products, antibodies, clotting proteins, chemical messengers such as hormones, and proteins that help maintain the body’s fluid balance.
  2. Red Blood Cells (erythrocytes): Red blood cells (RBCs) are the most abundant cell in the blood. RBCs contain a special protein called hemoglobin (Hgb), which helps carry oxygen (O2) from the lungs to the rest of the body and then returns carbon dioxide (CO2) from the body to the lungs so it can be expelled. Blood appears red because of the large number of red blood cells, which get their color from the hemoglobin.
  3. White Blood Cells (leukocytes): White blood cells (WBCs) protect the body from infection. They are much fewer in number than red blood cells, accounting for about 1% of your blood.
    • The most common type of white blood cell is the neutrophil (a granulocyte), which is the “immediate response” cell and accounts for 55 to 70 percent of the total white blood cell count.
    • The other major types of white blood cells are the monocytes and lymphocytes. Both monocytes and lymphocytes are important in immune function. Monocytes also have a major role in wound healing, which will be discussed, below.
    • Lymphocytes are less involved in the wound healing response. However, to complete the educational discussion…There are two main populations of lymphocytes. T lymphocytes help regulate the function of other immune cells and directly attack various infected cells and tumors. B lymphocytes make antibodies, which are proteins that specifically target bacteria, viruses, and other foreign materials.
  4. Platelets (thrombocytes): Unlike RBCs and WBCs, platelets (plts) are not actually cells but rather small fragments of cells. Platelets help the blood clotting process by gathering at the site of an injury, sticking to the lining of the injured blood vessel, and forming a platform on which blood coagulation (clotting) can occur. This results in the formation of a fibrin clot (like a nutritious, sticky plug), which covers the wound and prevents blood from leaking out. This fibrin clot forms the initial scaffolding upon which new tissue forms, thus promoting healing.

Understanding the phases of wound healing

Now that we have been introduced the components of our blood, we can begin to understand how those blood components are vital to the wound healing process. A relatively simple example to help absorb the basic fundamentals of wound healing, is falling and cutting the skin over your knee. What happens in the body to heal that cut or scrape?

…There are four stages of wound healing that the body carries out from the time you scrape your knee, until the formation of the mature scar, months later…

  1. Clotting
    • Clotting is formally known as hemostasis. This is the initial clotting of the scrape to stop the bleeding. The process takes seconds to minutes.
    • Adhesion: Platelets are our “clotting” cells (or cell fragments), that stick to the injured site.
    • Activation: After adhesion, platelets change shape and release natural chemical signals to promote clotting (they call in their teammates). When the specialized proteins (enzymes) are activated, a complex cascade of events takes place and, in the end, the glycoprotein fibrinogen is converted into fibrin. The fibrin then forms a mesh and acts as “glue” to bind platelets to each other. The result is a fibrin “clot”, which acts as a scaffold for other cells to attach to (infiltrate or invade) and build upon (proliferate or grow).
  2. Inflammation
    • This process takes hours to days. This involves recruitment of the second and third wave of cells in the blood to a) clean up the work site and b) start building a stronger, more complex clot or scab.
    • As per the title, the next cells to get involved are your inflammatory cells, your white blood cells (WBCs). One type of WBC is a neutrophil. Neutrophils “kill and clean”. In the clean-up process, neutrophils will recruit more WCBs (they call in their cousins). The neutrophils will send out more chemical messengers which call in the second line of WCBs called monocytes (cousins).
      1. *For those reading this article who have a science background; the neutrophils release inflammatory mediators TGF-B1, IL-1, IL-4 in order to call in the monocytes
    • Monocytes will change into macrophages (the medical term is “differentiate” which means to become more specialized), which are like little Pac-Man messengers that eat up (the medical term is “phagocytosis”) damaged/dead cells and clear them out, along with bacteria and other debris.
    • There is a third wave of recruitment: More chemical messengers are released and proteins called growth factors (GFs) are released into wound.
    • Growth factors are vital to the healing process!! These growth factors have two important jobs:
      1. GFs promote further migration of cells to the area (even more recruitment of important teammates!)
      2. GFs promote division of cells during proliferative phase (I.e. GFs promote the actual process of cell division for REGENERATION).
  3. Proliferation (Replication and division of cells for “growth”)
    • This phase takes days to weeks. Proliferation is complex. There are many different processes going on at the same time.
    • The WBCs are still important. The macrophages keep releasing chemical messengers (the medical term is “cytokines”) and GFs to boost the process of building new blood vessels (the medical term is “angiogenesis”) and the building of the fresh fibrous tissue (the medical term is “fibroplasia”).
    • The collagen cells (fibroblasts) replicate and then synthesize new components of scar tissue (called the extracellular matrix – ECM). Simply put…the scaffolding that was initiated with the fibrin clot gets reinforced and replaced with higher quality tissue.
    • The blood vessels that have been growing into the fresh tissue start to help out with the process. They bring oxygen and nutrients necessary for the metabolism and growth of cells into the tissue.
    • Essentially, the wound is being filled in by fresh scab tissue. Doctors call this “granulation tissue”. Granulation tissue is new connective tissue (fibrous tissue) and microscopic blood vessels that form on the surfaces of a wound during the healing process (the weak scab, the fibrin clot gets replaced with a strong scab, granulation tissue). 
  4. Maturation/Remodeling
  5. The scab matures. Depending on the regenerative capacity of the tissue (location and type of injury in the body) the body will achieve various outcomes:
    1. The scab may begin its journey to becoming a mature scar.
    2. If the tissue environment is suitable, the scab may be replaced by new tissue, identical to the original cells in the region.
  6. During this final stage, blood vessels formed in the scab (granulation tissue) are no longer required and are removed by apoptosis (organized cell death and removal).
  7. The body begins to remove the less useful collagen and replace it with stronger, more structured collagen.