Summary
Platelet-rich plasma (PRP) is a new powerful biological tool in sports medicine, when used to treat tendon, ligament and muscle injuries. PRP is a fraction of autologous whole blood containing an increased number of platelets and a wide variety of cytokines that can improve and accelerate the healing of various tissues.
An analysis of the literature shows promising pre-clinical results for PRP treatment, but there is a lack of solid clinical proof to support its use in sports medicine, and in fact, clinical findings on individual responses to PRP treatment are contradictory. These contradictions may be due to interindividual differences in the presence of single nucleotide polymorphisms (SNPs) in genes related to PRPs and/or their receptors. These SNPs can determine a greater or lesser response to this treatment and consequently a shorter or longer recovery time.
We have focused our attention in the study of genes related to PRP with the aim to develope a genetic profile that will identify the individuals and injuries most likely to benefit from PRP treatment.
Keywords: musculoskeletal soft-tissue injuries, single nucleotide polymorphisms, platelet-enriched proteins, growth factors
Introduction
Since PRP was first introduced as topical adjuvant therapy to treat chronic leg ulcers in the late 1980s1, its use has been extended to many fields of medicine, such as dermatology, ophthalmology2, dentistry3 and maxillofacial surgery3. Recently, PRP injections have emerged as a fashionable non-invasive treatment also in sports medicine4, where they are used to treat acute or chronic tendinopathy5–8 and muscle9,10 and ligament11,12 injuries, because PRP provides numerous growth factors needed to promote the healing process. Despite the wide use of PRP injections, research into their clinical efficiency is still in its beginings, and an analysis of the literature reveals a lack of solid evidence supporting the use of PRP13. More studies are required to confirm preliminary results and provide stronger scientific evidence.
Tissue repair in musculoskeletical injuries is often a slow and sometimes incomplete process. Musculoskeletical injuries have a great impact on athletes – especially elite athletes – and a rapid recovery of full efficiency and return to competition is of primary importance14. The search for a minimally invasive treatment of these injuries is of great importance, especially in the world of sports.
The use of growth factors is thought to be useful in clinical practice15 because it promotes rapid healing with a high-quality tissue and allows an early and safe return to unrestricted activity. Platelet-rich plasma (PRP) is a simple and minimally invasive way to obtain a natural concentration of autologous growth factors, including IGF, EGF, TGFb1, FGF216, as growth factors are critical for wound healing. PRP is currently being widely experimented in different fields of medicine due to its ability to help the regeneration of tissue with low healing potential. The analysis of the literature17,18 shows promising pre-clinical results but contradictory clinical findings in individual response to treatment in sports injuries. These contradictions may be due to interindividual differences in the presence of single nucleotide polymorphisms (SNPs) in genes related to PRP and/or their receptors and that these SNPs can determine a greater or lesser response to treatment and consequently a shorter or longer recovery time. A SNP is a DNA sequence variation which occurs when a single nucleotide in the genome differs in similar chromosomes in a given individual. SNPs in genes related to the biology of muscles19,20, tendons21–23 and ligaments24 have been associated with injury recovery time25,26.
Questions about PRPs and hypothesis
In recent years there has been an increasing research into genes related to the healing of soft tissue27. SNPs in genes that codify for these growth factors could influence treatment effectiveness and explain differences observed in recovery times. It is important to examine the maximum possible number of SNPs in PRP-related genes in order to identify a gene signature that promotes tissue healing in order to determine an objective measurement of an individual’s predisposition to recovery after this kind of treatment. Moreover it is important to know if the presence of these SNPs correlates with a greater or lesser degree of injury repair capability and/or with a short or long recovery time and, finally to identify a genetic profile for the selection of individuals who will respond more quickly to treatment following musculoskeletal soft tissue injuries and to identify the type of injury (muscle, tendon or ligament) in which PRP treatment is most effective.
Why analyze PRPs?
Cytokines and growth factors are soluble signaling proteins affecting the process of normal wound healing28. Cytokines control the inflammatory phase that clears cellular and extracellular matrix debris. The inflammatory stage is guided by inflammatory cells that release multiple cytokines, including IL-1. Cytokines induce expression of fibroblasts and endothelial cells and cause macrophage expression of more cytokines. As inflammation reduces, wound repair takes place29. Early wound repair includes three simultaneous steps (epithelization, neoangiogenesis and pre-matrix formation) and is controlled by growth factors (platelet-derived growth factor [PDGF], keratinocyte growth factor, and transforming growth factor β). Finally, during the later wound repair, TGFb up regulates MMPs inhibitors to help matrix construction by driving collagen expression.
Due to the high implication of these molecules in this important process, we think it is important to analyze the presence of SNPs in all of these factors to elucidate if these polymorphisms could affect the final protein function. The most commonly studied platelet proteins include platelet-derived growth factor (PDGF), transforming growth factor (TGF-β), platelet-derived epidermal growth factor (PDEGF), vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), fibroblastic growth factor (FGF), epidermal growth factor (EGF)30 (Tab. 1).
Table 1.
Growth factors and their associated role.
| GROWTH FACTOR | POSSIBLE ROLE |
|---|---|
| PDGF | Angiogenesis Collagen synthesis |
| TGFB | Collagen type I synthesis Fibronectin synthesis Fibroblasts proliferations |
| PDEGF | Cellular proliferation and differentiation |
| VEGF | Vascularization |
| IGF-1 | Stimulates protein synthesis |
Future Goals
The use of PRP treatment has increased in a somewhat random manner without real knowledge of its effectiveness, since contradictory results have been reported. The study of these SNPs may shed light on the tendency of certain individuals to recover more rapidly and more completely from injuries and may help identify individuals with an enhanced injury repair system.
Now our research group is investigating this issue with a group of professional football players from the Spanish League with promising results and shortly we will be able to increase our sample size with players from European teams.
Future findings will provide a tool to identify the individuals and injuries most likely to benefit from PRP treatment and thus improve not only recovery time but also restitutio ad integrum by reducing the risk of re-injury and scars production.
The study meets the ethical standards of the Journal31.
Acknowledgments
Many thanks are given to Prof. Nicola Maffulli for the help given in preparing the present manuscript and to Manel Garcia from FC Barcelona Medical Services.
References
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