There are several methods for preparing platelet-rich plasma, and they differ in the concentration of platelets in the plasma to be injected. Most devices currently used to prepare plasma have a concentration of 3 to 5 times that. According to at least one study (out of several laboratory studies), this percentage is considered high and harms the injured tendon instead of stimulating healing and recovery. Is this study accurate and correct? Is it possible that injecting platelet-rich plasma at this concentration causes harm to the tendons? Is injecting plasma at a high concentration for tendon inflammation and rupture really beneficial or harmful? However, with the existence of many clinical studies on patients who were treated in this way and their results were positive, if this percentage was harmful, all of these clinical studies would have failed. Therefore, in this article, we will discuss several laboratory studies in this regard related to the concentration of platelets in plasma. It can be said that there are two groups of research that conflict with each other in their results. The first group concluded that medium or high concentrations of platelet-rich plasma are harmful to tendons and do not increase healing stimulation for damaged and inflamed tendons. The second group concluded that the opposite is true, as the higher the concentration of platelet-rich plasma, the greater the rate of healing stimulation for damaged and inflamed tendons. Given this discrepancy in the results of the studies, which results are considered more accurate or more reliable? We visited our colleagues at the Interventional Orthopaedic Foundation (IOF) Research Center at its conference in Denver in early 2017, which focused its research on the differences in the results of these studies and concluded the following about the two groups.
The first group: Injection of platelet-rich plasma at a high concentration is harmful to tendons
The most famous of these studies is the study by the Italian researcher Giusti[1], which concluded that if the plasma concentration exceeds 1-2 times, this will lead to the opposite result by not stimulating tendon cells to heal, and that the concentration level reaching 3-5 times causes significant death of tendon cells. If you look closely at this conclusion, it means that all plasma injections are harmful to tendons, as most of the devices currently used to prepare plasma range from 3 to 5 times the concentration. The following image explains the principle of the laboratory study.
From the image, it is noted that the higher the plasma concentration, the more adverse the results. There are also other studies that had the same conclusion, such as the study by researcher Russell[2], which also concluded that the higher the plasma concentration, the more damage it caused to tendon cells.
The second group: Injection of platelet-rich plasma at a high concentration is beneficial for tendons
One of the most famous of these studies is the study by the Korean researcher Jo[3], which included a number of different tissues, including tendon tissue. The study concluded that the higher the concentration of platelet-rich plasma, the more stimulation of healing and recovery of the damaged tissue. This contradicts the studies of the first group. The following image explains the principle of the laboratory study.
From the image, it is noted that the higher the plasma concentration, the more positive the results, and there are also other studies that had the same conclusion, such as the study by researcher Anitwa[4].
So why this difference and conflict in the results? What are the correct conclusions? To answer that, we need to look at the design of each study and how it was done to reach its conclusions!
Reviewing the design of the studies for the first and second groups
The Interventional Orthopedics Foundation (IOF) Research Center studied the design of the studies for the two groups[5], as in these two groups of studies, the cells were grown in the laboratory through two basic elements for their survival, which are: food and stimulants (such as fertilizer, to simplify understanding). The study concluded that the design of the studies for the first group contains a defect in relation to these two elements, which we explain as follows:
1. Cell food consists of elements that are considered an essential factor for cell growth (MEM), including:
Inorganic salts (Na+, K+, Ca2+).
Carbohydrates (glucose).
Amino acids.
Vitamins (vitamin B group).
Bicarbonate acid solution and carbon dioxide.
2. The stimuli were composed of platelets derived from plasma, which contain:
Growth factors (FGF, PDGF, TGFB, VEGF)
Fibronectin
Metabolite transport proteins
By analyzing the studies of the first group, we see that the flaw in the design of the studies of the first group lies in the fact that the ratio of food to the ratio of stimuli was not consistent. In the studies of the first group, whenever the plasma concentration was increased (increased stimuli), the concentration of food for the cells was reduced (the ratio of food was not increased in a consistent manner with the stimuli), and this decrease led to a decrease in the ratio of food for the cells, which caused their death. Therefore, attributing the cause of cell death to the increase in the plasma concentration ratio is inaccurate, as it is due to the low ratio of food needed by the cells, which was not increased directly with the increase in the concentration of stimuli.
After analyzing the studies of the second group, it became clear that the design of the study aimed to maintain the ratio of food to the ratio of stimuli in a direct and constant manner. Accordingly, the results of these studies were inconsistent with the results of the studies of the first group.
Abstract
A laboratory study was conducted at the Research Center of the Interventional Orthopedics Foundation (IOF) to analyze these two groups of studies, and it was concluded that indeed the higher the concentration of platelets in the plasma, the better the results of stimulating cells to heal and recover, and this is also what we have seen from many clinical studies of many patients. If the results of the studies of the first group were correct, and knowing that most of the devices currently used to prepare plasma range from 3 to 5 times the concentration, the results would have been that all clinical studies on patients led to Adverse results and damage to the tendon tissues of patients. However, clinical studies have shown the opposite! Therefore, the second group studies had a more precise design and more valid results, and that the concentration of platelet-rich plasma is an influential factor in increasing the rate of improvement and the rate of stimulating healing and self-healing of the damaged tissue.
References
[1] Giusti, I., et al. “Platelet Concentration in Platelet-Rich Plasma Affects Tenocyte Behavior In Vitro.” BioMed Research International (2014)
[2] Russell, K.A. & Koch, T.G. “Equine platelet lysate as an alternative to fetal bovine serum in equine mesenchymal stromal cell culture—too much of a good thing?” Equine Vet J 48, 261–264 (2015).
[3] Jo, C.H., Kim, J.E., Yoon, K.S. & Shin, S. “Platelet-rich plasma stimulates cell proliferation and enhances matrix gene expression and synthesis in tenocytes from human rotator cuff tendons with degenerative tears.” Am J Sports Med 40, 1035–1045 (2012).
[4] Anitua, E., et al. “Fibroblastic response to treatment with different preparations rich in growth factors.” Cell Prolif 42, 162–170 (2009).
[5] Manuscript under review Other references Choi, B.H., et al. “Effect of platelet-rich plasma (PRP) concentration on the viability and proliferation of alveolar bone cells: an in vitro study.” Int J Oral Maxillofacial Surg 34, 420–424 (2005).
Fliefel, R., et al. “Mesenchymal stem cell proliferation and mineralization but not osteogenic differentiation are strongly affected by extracellular pH.” J Croniomaxillofacial Surg 44, 715–724 (2016).
Mishra, A., et al. “Buffered platelet-rich plasma enhances mesenchymal stem cell proliferation and chondrogenic differentiation.” Tissue Engineering Part C: Methods 15, 431–435 (2009).
Wuertz, K., Godburn, K. & Iatridis, J.C. “MSC response to pH levels found in degenerating intervertebral discs.” Biochem Biophys Res Commun 379, 824–829 (2009).
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