Abstract
Dear Editor,
We read with great interest the article titled “Platelet-Rich Plasma Does Not Inhibit Inflammation or Promote Regeneration in Human Osteoarthritic Chondrocytes In Vitro Despite Increased Proliferation” by Rikkers et al 1 in the September 2020 issue of this journal. The use of platelet-rich plasma (PRP) in knee osteoarthritis (OA) has really exploded in the last decade or so. Though enough clinical evidence exists in this regard, good-quality in vivo and in vitro studies offering information of the effects of PRP in joint milieu are few. We would like to appreciate the authors for a well-thought and well-conducted study that offers insight into the effects of PRP on human osteoarthritic chondrocytes. However, we would like clarify a few points regarding the study and offer our viewpoint on the same.
The donors used for chondrocytes in the study were the redundant material from total knee arthroplasty. The novelty of this study is that the authors have tried to culture the chondrocytes from osteoarthritic knee cartilage, and they have demonstrated that PRP has no effect in terms of inhibiting inflammation or promoting regeneration. This again proves the fact that PRP does not act in advanced OA stages. The best results of PRP are seen in early stages of knee OA, and multiple randomized controlled trials have established the clinical efficacy in early OA knee/early degenerative chondropathy. In fact, the literature supports for the use of PRP in early stages and not in advanced stages. 2 Previous in vitro studies have used healthy cartilage as source of chondrocyte culture 3 and have demonstrated anti-inflammatory and cartilage promoting effects. If we are to analyze previous studies and the present study, the right conclusion is that PRP has anti-inflammatory effects and chondro-protective effects in early OA and not in advanced OA.
The knees that undergo total knee arthroplasty generally have an advanced OA in one of the compartments (mostly medial). The cartilage in the other compartments may not be affected at all. The authors have stated that they pooled all the available cartilage from each donor. How is this sample representative of human osteoarthritic chondrocytes when the normal and abnormal cartilage has been mixed together? A comparison of the effects of PRP on chondrocyte cultures from different grades of OA would have given better insights into how PRP influences chondrocytes.
The effectiveness of PRP in early OA knee in terms of pain relief and functional improvement is best attributed to its anti-inflammatory effects, and previous studies have focused on synovium as the primary site of action of anti-inflammatory effect.4,5 Cartilage is usually studied for chondrogenesis and extracellular matrix production. Studies similar to the present one, if carried out on the synovium of advanced OA knees, may be a fruitful and a worthwhile experience, in order to truly demonstrate absence of anti-inflammatory effects. There are a few clinical trials that have demonstrated pain relief with PRP use in advanced stages of OA 6 and that could be due to PRP effects on synovium, which we believe to be the main site of action.
The details for the in vitro degradation profile for the fibrin and PRP gels must be highlighted. The PRP gels when activated with calcium chloride result in a burst of growth factors and they tend degrade early 7 and may not last 28 days when evaluations are carried out. So, data on degradation profiles of these gels will give more clarity on the results that were found. In such a scenario, with the dilution and early degradation of PRP gels coming into picture, multiple applications of PRP can be an option worth considering. The superiority of multiple applications of PRP over single application has been shown in animal studies 4 as well as clinical studies, 8 especially with respect to effects on the cartilage.
The PRP concentration used in the study is approximately 2 times the baseline. Similar studies have used platelet concentrations in the range of 4 to 6 times the baseline.3,9 This low concentration of platelets combined with dilution at various stages in the form of low concentration of PRP used, addition of activator, and diluted fibrinogen and thrombin component may have resulted in low concentration of growth factors, which may have affected the results.
The title is a negative reflection of PRP for normal average readers who may misinterpret the message that PRP has no anti-inflammatory effects in knee OA (after all it is human nature to get attracted to negative papers). Recall the editorial wherein PRP was called product rich in placebo, 10 and quickly caught the attention of all readers and is widely quoted in conferences and debates by PRP antagonists. The message out of this paper is that PRP does not have anti-inflammatory effects in cartilage of advanced stages of OA. This should be read and interpreted with caution. There are a number of randomized controlled trials and meta-analysis11-13 available today after 10 years of extensive research in this field to state that PRP is more effective than placebo and hyaluronic acid for early OA of the knee in terms of functional and pain scores.
So, we conclude by saying that “PRP is more than placebo-rich plasma”.