scholarly journals In vitro responses to platelet-rich-plasma are associated with variable clinical outcomes in patients with knee osteoarthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Habib Zahir ◽  
Bijan Dehghani ◽  
Xiaoning Yuan ◽  
Yurii Chinenov ◽  
Christine Kim ◽  
...  

AbstractAutologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA). However, the clinical outcomes after PRP administration are often variable, and there is limited information about the specific characteristics of PRP that impact bioactivity and clinical responses. In this study, we aimed to develop an integrative workflow to evaluate responses to PRP in vitro, and to assess if the in vitro responses to PRP are associated with the PRP composition and clinical outcomes in patients with knee OA. To do this, we used a coculture system of macrophages and fibroblasts paired with transcriptomic analyses to comprehensively characterize the modulation of inflammatory responses by PRP in vitro. Relying on patient-reported outcomes and achievement of minimal clinically important differences in OA patients receiving PRP injections, we identified responders and non-responders to the treatment. Comparisons of PRP from these patient groups allowed us to identify differences in the composition and in vitro activity of PRP. We believe that our integrative workflow may enable the development of targeted approaches that rely on PRP and other orthobiologics to treat musculoskeletal pathologies.

2017 ◽  
pp. 63-69
Author(s):  
George Chang Chien

Osteoarthritis (OA) is a progressive joint disease associated with both mechanical and biologic abnormalities of the articular cartilage and subchondral bone. In normal cartilage, a delicate balance exists between matrix synthesis and degradation; in OA, however, cartilage degradation exceeds synthesis. Treatment modalities include nonpharmacological, pharmacological, and surgical approaches. Intrarticular platelet rich plasma (PRP) has emerged as promising treatment for early stages of knee OA. PRP is an autologous blood product defined as a volume of plasma that has a supraphysiologic platelet count. PRP can accelerate the physiological recovery process, relieve pain, and contains anti-inflammatory and anti-bacterial activity. Although the mechanisms for these complex interactions are not completely understood, they are attributed to the more than 30 bioactive proteins contained in the alpha granules of platelets including growth factors and proteins, such as fibrin, fibronectin, vitronectin and thrombospondin. Several studies now have demonstrated that intraarticular PRP injections are safe and effective treatment to reduce pain and improve quality of life through increased function in knee OA. The available literature suggests that PRP is a better option than hyaluronic acid for many knee OA patients. We identified 12 comparative studies that demonstrated superiority of PRP as compared to hyaluronic acid for knee OA. Considering what is known about the deleterious effects of local anesthetic and corticosteroids on soft tissue health, it may be time for a shift in the knee OA treatment algorithm to favor early intervention for regenerative therapies including platelet rich plasma. Key words: Platelet rich plasma, hyaluronic acid, knee pain, knee osteoarthritis, arthritis, chondrotoxicity


Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1193
Author(s):  
Oliver Dulic ◽  
Predrag Rasovic ◽  
Ivica Lalic ◽  
Vaso Kecojevic ◽  
Gordan Gavrilovic ◽  
...  

Background: In the last decade, regenerative therapies have become one of the leading disease modifying options for treatment of knee osteoarthritis (OA). Still, there is a lack of trials with a direct comparison of different biological treatments. Our aim was to directly compare clinical outcomes of knee injections of Bone Marrow Aspirate Concentrate (BMAC), Platelet-rich Plasma (PRP), or Hyaluronic acid (HA) in the OA treatment. Methods: Patients with knee pain and osteoarthritis KL grade II to IV were randomized to receive a BMAC, PRP, and HA injection in the knee. VAS, WOMAC, KOOS, and IKDC scores were used to establish baseline values at 1, 3, 6, 9, and 12 months. All side effects were reported. Results: A total of 175 patients with a knee osteoarthritis KL grade II-IV were randomized; 111 were treated with BMAC injection, 30 with HA injection, and 34 patients with PRP injection. There were no differences between these groups when considering KL grade, BMI, age, or gender. There were no serious side effects. The mean VAS scores after 3, 7, 14, and 21 days showed significant differences between groups with a drop of VAS in all groups but with a difference in the BMAC group in comparison to other groups (p < 0.001). There were high statistically significant differences between baseline scores and those after 12 months (p < 0.001) in WOMAC, KOOS, KOOS pain, and IKDC scores, and in addition, there were differences between these scores in the BMAC group in comparison with other groups, except for the PRP group in WOMAC and the partial IKDC score. There were no differences between the HA and PRP groups, although PRP showed a higher level of clinical improvement. Conclusions: Bone marrow aspirate concentrate, Leukocyte rich Platelet Rich Plasma, and Hyaluronic acid injections are safe therapeutic options for knee OA and provide positive clinical outcomes after 12 months in comparison with findings preceding the intervention. BMAC could be better in terms of clinical improvements in the treatment of knee OA than PRP and HA up to 12 months. PRP provides better outcomes than HA during the observation period, but these results are not statistically significant. More randomized controlled trials and high quality comparative studies are needed for direct correlative conclusions.


2021 ◽  
pp. 036354652199801
Author(s):  
Michael R. Baria ◽  
W. Kelton Vasileff ◽  
James Borchers ◽  
Alex DiBartola ◽  
David C. Flanigan ◽  
...  

Background: Platelet-rich plasma (PRP) and hyaluronic acid (HA) are injectable treatments for knee osteoarthritis. The focus of previous studies has compared their efficacy against each other as monotherapy. However, a new trend of combining these 2 injections has emerged in an attempt to have a synergistic effect. Purpose: To systematically review the clinical literature examining the combined use of PRP + HA. Design: Systematic review. Methods: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using PubMed and Embase. The following search terms were used: knee osteoarthritis AND platelet rich plasma AND hyaluronic acid. The review was performed by 2 independent reviewers who applied the inclusion/exclusion criteria and independently extracted data, including methodologic scoring, PRP preparation technique, HA composition, and patient-reported outcomes (PROs). Results: A total of 431 articles were screened, 12 reviewed in full, and 8 included in the final analysis: 2 case series, 3 comparative, and 3 randomized studies. Average follow-up was 9 months. The modified Coleman Methodology Score was 38.13 ± 13.1 (mean ± SD). Combination therapy resulted in improved PROs in all studies. Of the comparative and randomized studies, 2 demonstrated that combination therapy was superior to HA alone. However, when PRP alone was used as the control arm (4 studies), combination therapy was not superior to PRP alone. Conclusion: Combination therapy with PRP + HA improves PROs and is superior to HA alone but is not superior to PRP alone.


2021 ◽  
Vol 22 (11) ◽  
pp. 5711
Author(s):  
Julian Zacharjasz ◽  
Anna M. Mleczko ◽  
Paweł Bąkowski ◽  
Tomasz Piontek ◽  
Kamilla Bąkowska-Żywicka

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world's population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.


2021 ◽  
Vol 22 (11) ◽  
pp. 5492
Author(s):  
Dawid Szwedowski ◽  
Joanna Szczepanek ◽  
Łukasz Paczesny ◽  
Jan Zabrzyński ◽  
Maciej Gagat ◽  
...  

Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.


2021 ◽  
Vol 49 (2) ◽  
pp. 487-496
Author(s):  
Yong-Beom Park ◽  
Jun-Ho Kim ◽  
Chul-Won Ha ◽  
Dong-Hyun Lee

Background: Although platelet-rich plasma (PRP) has potential as a regenerative treatment for knee osteoarthritis, its efficacy varies. Compositional differences among types of PRP could affect clinical outcomes, but the biological characterization of PRP is lacking. Purpose: To assess the efficacy of intra-articular PRP injection in knee osteoarthritis as compared with hyaluronic acid (HA) injection and to determine whether the clinical efficacy of PRP is associated with its biological characteristics. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 110 patients with symptomatic knee osteoarthritis received a single injection of leukocyte-rich PRP (1 commercial kit) or HA. Clinical data were assessed at baseline and at 6 weeks and 3 and 6 months after injection. The primary endpoint was an improvement in the International Knee Documentation Committee (IKDC) subjective score at 6 months, and the secondary endpoints were improvements in scores based on the Patient Global Assessment, the visual analog scale (VAS) for pain, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Samsung Medical Center patellofemoral score. Cell counts and concentrations of growth factors and cytokines in the injected PRP were assessed to determine their association with clinical outcomes. Results: PRP showed significantly improvement in IKDC subjective scores at 6 months (11.5 in the PRP group vs 6.3 in the HA group; P = .029). There were no significant differences between groups in other clinical outcomes. The Patient Global Assessment score at 6 months was better in the PRP group ( P = .035). The proportion of patients who scored above the minimal clinically important difference (MCID) for VAS at 6 months was significantly higher in the PRP group ( P = .044). Within the PRP group, the concentrations of platelet-derived growth factors were high in patients with a score above the MCID for VAS at 6 months. The incidence of adverse events did not differ between the groups ( P > .05). Conclusion: PRP had better clinical efficacy than HA. High concentrations of growth factors were observed in patients who scored above the MCID for clinical outcomes in the PRP group. These findings indicate that concentration of growth factors needs to be taken into consideration for future investigations of PRP in knee osteoarthritis. Registration: NCT02211521 (ClinicalTrials.gov identifier).


Author(s):  
Ekin İlke Şen ◽  
Mustafa Aziz Yıldırım ◽  
Tuğba Yeşilyurt ◽  
Fatma Nur Kesiktaş ◽  
Demirhan Dıraçoğlu

Author(s):  
Vandana Menon ◽  
Caroline Huber ◽  
Alexandria Portelli ◽  
Marissa Baker-Wagner ◽  
Scott Kelley ◽  
...  

ObjectivesKnee osteoarthritis (OA) is a leading cause of health-related disability. In the absence of curative non-operative therapies, treatment goals are limited to symptom relief. Data are limited on how patients and physicians prioritise available treatment options. We assessed patients’ preferences for and physicians’ attitudes towards intra-articular treatments including corticosteroids (IACS), an extended-release corticosteroid (TA-ER) and hyaluronic acids (IAHA).MethodsWe conducted a prospective, IRB-exempt, double-blind survey of patients with and providers who treat knee OA. Respondents were required to have received or prescribed TA-ER in a non-trial setting. We evaluated patients’ OA history, impact of knee OA and treatment preferences, and physicians’ decision-making and prescribing experiences.ResultsOf the 97 patient participants, mean age was 56 years, 70.0% were women, 75.0% had bilateral knee OA and 46.4% were diagnosed over 5 years ago. Of the 50 physician participants, 34.0% were rheumatologists, 42.0% were orthopaedic surgeons and 60.0%, on average, treat 50+ patients with knee OA per month. Treatment selection factors considered ‘very important’ to patients and physicians included disease severity (88.7%, 82.0%), impact on quality of life (88.7%, 72.0%), disease extent (84.5%, 54.0%) and activity level (80.4%, 64.0%). A majority (93.8%) of patients indicated moderate to severe difficulty with their knees. Fewer patients (76.3%) reported shared decision making compared with physicians (92.0%). Half (50.5%) of the patients reported that they experienced months of pain relief with TA-ER, 27.7% with IACS and 18.8% with IAHA. Physician assessments were consistent but estimated a greater duration of treatment effects than that reported by patients across all therapies.ConclusionWhile knee OA has a tremendous impact on patients, there are significant unmet treatment needs. The increasing use of patient-reported outcomes will allow patients and physicians to track pain and functional status over time and across therapies, improving shared decision-making.


2016 ◽  
Vol 38 (3) ◽  
pp. 1245-1256 ◽  
Author(s):  
Shuo Chen ◽  
Lei Zhang ◽  
Ruonan Xu ◽  
Yunfan Ti ◽  
Yunlong Zhao ◽  
...  

Background/Aims: The bradykinin B2 receptor (BDKRB2) +9/-9 gene polymorphisms have been shown to be associated with the susceptibility and severity of osteoarthritis (OA); however, the underlying mechanisms are unclear. In this study, we investigated the correlation between the BDKRB2 +9/-9 polymorphisms and pro-inflammatory cytokine levels in OA and the molecular mechanisms involved. Methods: A total of 156 patients with primary knee OA and 121 healthy controls were enrolled. The BDKRB2 +9/-9 polymorphisms were genotyped. The tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 levels were determined using Enzyme-linked immunosorbent assay (ELISA). The toll-like receptor (TLR)-2 and TLR-4 mRNA levels were determined by quantitative real-time PCR. The basal and bradykinin-stimulated pro-inflammatory cytokine secretion in human OA synoviocytes and the involvement of TLR-2 and mitogen-activated protein kinases (MAPKs) were investigated. Results: The presence of -9 bp genotype is associated with higher TNF-α, IL-6, and IL-8 levels and higher TLR-2 expression in OA patients. The basal and bradykinin-induced TLR-2 expressions in human OA synoviocytes were significantly reduced by specific inhibitors of p38, JNK1/2, and ERK1/2. Both the B2 receptor antagonist MEN16132 and TLR-2 silencing inhibited IL-6 and IL-8 secretion in human OA synoviocytes. Conclusion: The data suggested that the BDKRB2 +9/-9 polymorphisms influence pro-inflammatory cytokine levels in knee osteoarthritis by altering TLR-2 expression.


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