The Science of PRP: How Platelet Rich Plasma Therapy Works

Platelet-rich plasma (PRP) therapy is an exciting treatment option used to treat musculoskeletal pain and promote regeneration of damaged tissues by injecting it directly into the target area. Utilizing a portion of the patient’s own blood, which is concentrated using the process of centrifugation, PRP works by dramatically increasing the amount of growth factors and immune-modulating cells compared to whole blood. 

What Are Platelets and Why Do They Promote Healing?

Platelets are small cells that travel through the bloodstream. They work as the primary mediators of clotting, or the process of sealing off damage to blood vessel walls. However, they are also important for tissue healing and regeneration. This is because platelets contain numerous growth factors and immune modulators released following platelet activation to rapidly respond to damaged vasculature and tissue. The release of these mediators promotes swift healing and signals other immune cells in the body to direct their actions to a specific damaged target area. For this reason, these immune cells are crucial to the regulation of inflammation and overall healing.

Brief Overview of Platelet’s Key Growth Factors and Immune Mediating Cells

A Platelet-Derived Growth Factor (PDGF) is a glycoprotein released at the site of the injury following platelet activation. PDGF activates signal proteins to stimulate collagen synthesis via fibroblast formation (a connective tissue-producing cell), angiogenesis (the process of forming new blood vessels and expanding existing vasculature), and the delivery of important immune cells, including macrophages and neutrophils to the site of injury2.

A Transforming Growth Factor-Beta (TGF-B) is a cytokine (signaling protein) released by activated platelets and functions to stimulate mesenchymal (undifferentiated) stem cell proliferation as well as collagen synthesis via fibroblast formation and angiogenesis3. Notably, mesenchymal stem cells are able to differentiate into multiple different types of cells involved in the production of cartilage, tendon, muscle, and bone4.

An Insulin-Like Growth Factor-1 (IGF-1) is a cytokine released by activated platelets similar in structure to insulin, which is the main anabolic growth factor involved in the production and maintenance of articular cartilage. IGF-1 functions to recruit chondrogenic (cartilage-making) cells and stimulates the proliferation of chondrocytes. Additionally, IGF-1 is important in the amplification of platelet activation, the recruitment of fibroblasts, and the stimulation of protein synthesis5.

Neutrophils are white blood cells (WBCs) essential in the first-line, rapid defense against invading pathogens. Neutrophils cause an increased inflammatory response in order to recruit other immune cells, as well as healing mediators, to sites of damaged tissue. This rapid, increased inflammatory response can result in minor discomfort in the few days following PRP injection but is necessary to enhance the delivery of healing factors to kickstart the formation of a regenerative environment in the target area6.

Lymphocytes are WBCs also involved in the immune response against invading pathogens. T-lymphocytes are directly involved in the attack on invading pathogens, and B-lymphocytes are involved in the production of antibodies. Additionally, lymphocytes aid in the differentiation of other immune cells, such as monocytes and macrophages, a process that has been found to contribute to tissue healing7.

What is Centrifugation, and How is it Used to Make PRP?

Centrifugation is a process in which particles in a solution are separated using centrifugal forces. A centrifuge is a machine in which a rotor spins a solution to separate components of the solution with centrifugal forces based on the components’ size, density, and viscosity. PRP utilizes centrifugation to separate a patient’s whole blood into three layers, including a top layer which is mostly plasma with very few platelets (also called platelet-poor plasma), a thin middle layer known as the “buffy coat” which is rich in WBCs and platelets, and a bottom layer of red blood cells. 

In order to concentrate the platelets even more, some kits use a second spin where the “buffy coat” is transferred to another tube and centrifuged again. At Desert Spine and Sports Physicians, we use this double spin technique in order to concentrate the platelets to at least 7x concentration compared to the baseline. This “platelet-rich plasma” is then injected into the target area8.

How Does Healing Occur Following a PRP Injection?

After a PRP injection, with concentrated platelets directed right into a damaged target area, the healing process begins with an inflammatory phase lasting up to one week. This inflammatory phase is crucial in recruiting and activating immune cells (such as neutrophils and lymphocytes), activating other platelets, and delivering key growth factors and other cytokines to the target area. The inflammatory phase is then followed by a proliferation phase at approximately day 5-20. During this phase, the platelets release growth factors such as PDGF, TGF-B, and IGF-1 to stimulate the recruitment of cells needed to heal damaged tissue such as fibroblasts, chondrocytes, osteoblasts, and mesenchymal stem cells. Once these cells are recruited to the target site, a remodeling phase occurs, which lasts 3-6 months and is characterized by the production of new collagen as well as cartilage, tendon, bone, and muscle. 

This process leads to sustained symptom relief for PRP-treated patients, with many studies showing positive effects of treatment lasting 1 to 2 years and likely beyond. Overall, PRP is a promising treatment option that not only relieves symptoms, but treats the underlying cause of those symptoms for improved pain and function. 

If you have any questions about PRP therapy, contact us at Desert Spine and Sports Physicians. Our Arizona-based physicians are Board-Certified in Physical Medicine and Rehabilitation (PM&R), Fellowship-Trained in Interventional Spine and Musculoskeletal Medicine, and are experts in using regenerative therapies such as PRP to treat pain and heal injury.   

References

1. Fountain JH, Lappin SL. Physiology, Platelet. [Updated 2023 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470328/
2. AUTHOR=Qian Yun , Han Qixin , Chen Wei , Song Jialin , Zhao Xiaotian , Ouyang Yuanming , Yuan Weien , Fan Cunyi  Platelet-Rich Plasma Derived Growth Factors Contribute to Stem Cell Differentiation in Musculoskeletal Regeneration; Frontiers in Chemistry, 2017; DOI=10.3389/fchem.2017.00089
3. Mary H. Branton, Jeffrey B. Kopp, TGF-β and fibrosis, Microbes, and Infection, Volume 1, Issue 15,1999, Pages 1349-1365, ISSN 1286-4579, https://doi.org/10.1016/S1286-4579(99)00250-6.
4. Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells – current trends and future prospective. Biosci Rep. 2015 Apr 28;35(2):e00191. doi: 10.1042/BSR20150025. PMID: 25797907; PMCID: PMC4413017.
5. Ingeborg Hers; Insulin-like growth factor-1 potentiates platelet activation via the IRS/PI3Kα pathway. Blood 2007; 110 (13): 4243–4252. doi: https://doi.org/10.1182/blood-2006-10-050633
6. Pitchford S, Pan D, Welch HC. Platelets in neutrophil recruitment to sites of inflammation. Curr Opin Hematol. 2017 Jan;24(1):23-31. doi: 10.1097/MOH.0000000000000297. PMID: 27820736; PMCID: PMC5421649.
7. Larosa DF, Orange JS. 1. Lymphocytes. J Allergy Clin Immunol. 2008 Feb;121(2 Suppl):S364-9; quiz S412. doi: 10.1016/j.jaci.2007.06.016. PMID: 18241683.
8. Dhurat, Rachita; Sukesh, MS. Principles and Methods of Preparation of Platelet-Rich Plasma: A Review and Author’s Perspective. Journal of Cutaneous and Aesthetic Surgery 7(4):p 189-197, Oct–Dec 2014. | DOI: 10.4103/0974-2077.150734