Types Of Platelet-rich Plasma Research Articles

Not all platelet-rich plasma are created equal.

This review aims to elucidate potential variations in clinical outcomes resulting from the use of different types of platelet-rich plasma (PRPs) in reproductive medicine. It seeks to explore the reasons behind the diverse results reported in various studies and assess the general features distinguishing different PRP formulations. PRPs have found applications across diverse medical fields, generating controversy due to the variability in outcomes. The field of reproductive medicine, despite its limited published studies, is encountering a similar challenge as it integrates these treatments. The multitude of PRP product brands in the market, coupled with 'home-made' PRPs, poses a significant barrier to establishing a common protocol for the preparation of standardized PRP products. This impediment hinders widespread adoption by clinicians, particularly in endometrial or ovarian treatments. Drawing from evidence in other medical disciplines, this review endeavors to compile essential characteristics that PRPs must possess, aiming to mitigate the impact of variables affecting results in forthcoming studies.

The current use of the regenerative properties of platelet-rich-plasma in different medical conditions with particular emphasis on gynecology and obstetrics

Abstract Platelet-rich-plasma (PRP) is a concentrate of plasma containing high levels of platelets and different growth factors, involved in various cellular and regenerative processes, i.a. wound healing and tissue regeneration. Currently, due to its regenerative properties, PRP is widely used in different medical conditions. This paper summarizes knowledge about types of PRP, its preparation and current possibilities of PRP treatment in many fields of medicine with a particular emphasis on gynecology and obstetrics.

Poster 223: Patient Reported Outcomes Following Treatment with Leukocyte Rich Platelet Rich Plasma Injections for Proximal Hamstring Tendinopathy

Poster 223: Patient Reported Outcomes Following Treatment with Leukocyte Rich Platelet Rich Plasma Injections for Proximal Hamstring Tendinopathy

Safety and efficacy of intra-articular injection of platelet-rich plasma for the treatment of ankle osteoarthritis: a systematic review and meta-analysis.

To evaluate the safety and efficacy of platelet-rich plasma (PRP) intra-articular injective treatments for ankle osteoarthritis (OA). A systematic literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in PubMed, Scopus, Embase, Google Scholar, and the Cochrane library until May 2022. Both randomized and non-randomized studies were included with the assessment of the risk of bias. We recorded the participant's age, gender, type of PRP, injection volume, the kit used, and activating agent. We subsequently assessed the short-term and long-term efficacy of PRP using the functional scores and visual analog scale (VAS). We included four studies with a total of 127 patients, with a mean age of 56.1years. 47.2% were male (60/127), according to eligibility criteria. There were three cohort studies and one randomized controlled trial (RCT) study, and no study reported severe adverse events. All included studies used the Leukocyte-poor PRP. Short-term follow-up results suggested significant improvement of the American Orthopaedic Foot and Ankle Society (AOFAS) score in the PRP injection group compared to the control group (n = 87 patients; MD: 6.94 [95% CI: 3.59, 10.29]; P < 0.01). Consistently, there was a statistical difference in AOFAS score between PRP injection and control groups in the final follow-up (≥ 6months) (n = 87 patients; MD: 9.63 [95% CI: 6.31, 12.94]; P < 0.01). Furthermore, we found a significant reduction in VAS scores in the PRP groups at both the short-term follow-up (n = 59 patients; MD, - 1.90 [95% CI, - 2.54, - 1.26]; P < 0.01) and the ≥ sixmonths follow-up (n = 79 patients; MD, - 3.07 [95% CI, - 5.08, - 1.05]; P < 0.01). The improvement of AOFAS and VAS scores at ≥ sixmonths follow-up reached the minimal clinically important difference (MCID). Nevertheless, the treatment effect of AOFAS and VAS scores offered by PRP at short-term follow-up did not exceed the MCID. Substantial heterogeneity was reported at the ≥ sixmonths follow-up in VAS scores (I2: 93%, P < 0.01). This meta-analysis supports the safety of PRP intra-articular injection for ankle OA. The improvements of AOFAS and VAS scores in the PRP group at short-term follow-up do not exceed the MCID to be clinically significant. PRP injection provides significant improvement of AOFAS score and reduced pain at ≥ sixmonths follow-up. The efficacy of PRP should be interpreted with caution regarding the high heterogeneity and the scarcity of available literature, which urges large-scale RCTs with longer follow-up to confirm the potential efficacy of PRP injection for ankle OA.

Platelet-rich plasma for the treatment of alopecia: a systematic review and meta-analysis.

The number of articles evaluating the efficacy of platelet-rich plasma (PRP) in androgenetic alopecia (AGA) and alopecia areata (AA) has increased exponentially during the last years. This systematic review and meta-analysis is aimed at evaluating the benefit of PRP in the treatment of alopecia. We searched MEDLINE (through PUBMED), Embase, and CENTRAL for relevant data. Treatment effect was described by mean difference (MD) and risk difference with 95% confidence intervals (CI). The GRADE system was used to assess the certainty of the body of evidence. We found 27 controlled trials (1,117 subjects) that met our inclusion criteria: 18 trials (713 subjects) in patients with AGA, and 9 (404 subjects) in patients with AA. Eleven studies had a split head design. There was heterogeneity in types of PRP (e.g., activated and non-activated) and administration schedules. PRP was compared to saline injections (18 studies), local steroid injections (4 studies) and other comparators (5 studies). Most commonly reported outcomes were hair density and hair regrowth. It was not possible to pool all outcome data because of heterogeneity in reporting, and because reporting was often limited to a single study. Compared to saline injections, PRP injections increased hair density over a medium-term follow-up (MD, 25.6 hairs/cm2; 95 % CI: 2.62-48.57), but the evidence was rated as low quality due to inconsistency and risk of bias. In individuals with AA, it is unclear whether PRP injection compared with triamcinolone injection increase the rate of subjects with hair regrowth (very-low quality of evidence due to inconsistency, imprecision, and risk of bias). There were no serious adverse events related to PRP injection or control treatments. There is limited evidence showing benefit of PRP for treatment of alopecia, and most of this evidence is of low quality.

Bone-Regenerative Ability of Platelet-Rich Plasma Following Sinus Augmentation with Anorganic Bovine Bone: A Systematic Review with Meta-Analysis.

Background: The objective of this systematic review is to assess the effect of the adjuvant use of platelet-rich plasma (PRP) and its type on new bone formation by anorganic bovine bone during maxillary sinus floor augmentation procedure. Methods: PubMed, Cochrane Central Register of Controlled Trials, and Ovid databases were searched for relevant studies published up to 16 September 2021. Randomized clinical trials (RCTs) and non-randomized controlled clinical trials (CCTs) that reported data on the new bone formation (measured by histomorphometric analysis) were considered. Risk of bias and quality assessment of included studies were evaluated following the Cochrane Handbook for Systematic Reviews of Interventions and the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Strength of evidence was assessed following the approach of the Agency for Healthcare Research and Quality (AHRQ) through its evidence-based practice center (AHRQ EPC). The meta-analysis was based on the primary outcome of newly formed bone, for which the standard mean difference was calculated. Results: After the application of eligibility criteria, six clinical trials (three RCTs and three CCTs) covering 85 maxillary sinus floor elevation procedures were included. The pooled new bone formation value for PRP was 1.67 (95% CI: −0.15 to 3.49; I2: 86%), indicating the absence of significant effect. Plasma rich in growth factors (PRGF) was the pure PRP tested in five of the included studies. When sub-group (type of PRP) meta-analysis was performed, significantly higher new bone formation was observed in the PRGF group [2.85 (95% CI: 0.07 to 5.64; I2: 88%)] in comparison to the control group. Conclusions: A beneficial effect on new bone formation after maxillary sinus floor elevation can be obtained when anorganic bovine bone is mixed with PRGF.

High-Throughput Proteomic Analysis of Human Dermal Fibroblast Response to Different Blood Derivatives: Autologous Topical Serum Derived from Plasma Rich in Growth Factors (PRGF) versus Leukocyte- and Platelet-Rich Plasma (L-PRP).

Platelet-rich plasma (PRP) is nowadays used in the treatment of different types of cutaneous lesions. However, different compositions can influence clinical outcomes. Among them, the inclusion of leukocytes is controversial. High-throughput proteomics techniques were used to analyze the proteins that are differentially expressed in human dermal fibroblasts (HDFs) after treatment for 24 h with two PRP types, autologous topical serum (Endoret serum—ES) derived from plasma rich in growth factors (PRGF) and leukocyte- and platelet-rich plasma (L-PRP). The identified proteins were then classified by both Gene Ontology and Ingenuity Pathway Analysis. The obtained results show that the compositions of ES and L-PRP differ in such a way that they induce different responses in HDFs. ES-treated HDFs overexpress growth factor-related proteins, leading to protein synthesis, cell proliferation and migration. By contrast, L-PRP treatment induces a response similar to that caused by proinflammatory molecules. These data could explain the contradictory clinical results obtained for the different types of PRP, especially with respect to their leukocyte contents.

A systematic review on the efficacy of different types of platelet-rich plasma in the management of lateral epicondylitis

Platelet-rich plasma (PRP) is reported as an effective treatment for lateral epicondylitis (LE). Theoretically, different types of PRP have different therapeutic effects. However, there is controversy on the effects of different types of PRP in the treatment of LE. The purpose of this study was to systematically compare pain relief, functional improvement, and the success rate of treatment using 2 different types of PRP by reviewing and summarizing the data available in the current literature on LE after PRP injection. The PubMed, MEDLINE, Embase, Cochrane Library, and Web of Science databases were reviewed. A computerized literature search was performed for related studies published from database inception to August 2021 using the following terms: lateral epicondylitis, tennis elbow, tendinopathy, lateral elbow pain, PRP, and platelet-rich plasma. The PRP patients included in our study were divided into those receiving leukocyte-poor PRP (LP-PRP) and those receiving leukocyte-rich PRP (LR-PRP) according to the different preparation methods. Outcomes of interest included patient characteristics, types and preparations of PRP, clinical outcomes, success rates, and the safety of treatment at short- and long-term follow-up. A total of 33 studies were evaluated in our analysis, including 2420 LE patients. LP-PRP was used in 19 of these studies, LR-PRP was used in 13, and both LP-PRP and LR-PRP were used in 1. Patients in both PRP groups showed significantly improved clinical outcomes after treatment compared with before treatment. The mean visual analog scale scores ranged from 6.1 to 8.0 before treatment, ranged from 1.5 to 4.0 at short-term follow-up, and ranged from 0.6 to 3.3 at long-term follow-up in the LR-PRP group. The mean visual analog scale scores ranged from 4.2 to 8.4 before treatment, 1.6 to 5.9 at short-term follow-up, and 0.7 to 2.7 at long-term follow-up in the LP-PRP group. The Disabilities of the Arm, Shoulder and Hand scores in the LR-PRP and LP-PRP groups ranged from 47.0 to 54.3 and 30.0 to 67.7, respectively, before treatment and ranged from 20.0 to 22.0 and 5.5 to 19.0, respectively, at long-term follow-up. The success rates in the LR-PRP and LP-PRP groups ranged from 70% to 100% and 36% to 100%, respectively. The complication rate was lower in the LP-PRP group (3.9%) than in the LR-PRP group (6.4%, P=.029), with the main complication being temporary pain after PRP treatment. PRP treatment demonstrated significant improvements in terms of pain relief and functional improvement in LE patients regardless of the type of PRP. There were no significant differences in pain relief and functional improvement between LR-PRP and LP-PRP. The main complication was temporary pain after PRP injection, and the complication rate in the LP-PRP group was lower than that in the LR-PRP group.

Dependence of Electric Pulse Mediated Growth Factor Release on the Platelet Rich Plasma Separation Method

Platelet rich plasma (PRP) has been explored for multiple clinical applications, including dentistry, orthopedics, sports medicine, diabetic foot ulcers, and cosmetic treatments. Topical applications of PRP typically use thrombin to induce platelet activation, which is accompanied by growth factor release and clotting of the PRP, prior to treatment. Injectable PRP treatments typically use non-activated PRP under the assumption that collagen at the site of the injury mediates platelet activation to ensure growth factor release in vivo. Ex-vivo electrical stimulation of platelets is emerging as a robust, easy to use, instrument-based PRP activation technique to facilitate growth factor release with or without clotting, while providing tunability of growth factor release, clot mechanical properties (when desired), and serotonin release from the dense granules. This paper briefly reviews the key results of the electrical activation of platelets and demonstrates successful growth factor release by electrical ex-vivo stimulation without clotting for three types of PRP separated from whole blood using available commercial kits: Harvest, EmCyte and Eclipse. While these three types of PRP feature a wide range of platelet and red blood cell content compared to whole blood, we demonstrate that pulsed electric fields enable growth factor release for all these biological matrices generated using whole blood from four human donors. These experiments open opportunities for using electrically stimulated PRP with released growth factors without clotting for injectable platelet treatments in relevant clinical applications.

The effect of leucocyte concentration of platelet-rich plasma on outcomes in patients with lateral epicondylitis: a systematic review and meta-analysis.

The concentration of leukocytes influences the quality of platelet-rich plasma (PRP). However, there is no consensus on which type of PRP based on the concentration of leukocytes is the best for lateral epicondylitis (LE). We systematically searched the MEDLINE, Embase, and Cochrane Library databases until March 1, 2020. Studies involving randomized controlled trials, patients with LE, and treatment with PRP injections were included. PRP was classified into leukocyte-poor (LP) PRP and leukocyte-rich (LR) PRP. LR-PRP was defined as PRP with a white blood cell concentration exceeding that of whole blood (4.0-10.0 per μL3), whereas LP-PRP was defined as PRP with a lower white blood cell concentration than that of whole blood. The efficacy of PRP was assessed using the visual analog scale (VAS) and success rates. Eleven randomized controlled trials (six involving LP-PRP and five involving LR-PRP) were eligible for inclusion in this review. Eight studies were included in the meta-analysis to evaluate the VAS score. Regarding short-term follow-up, there was no difference in the VAS scores between the LP-PRP and control groups (standard mean difference [SMD], 0.01; 95% confidence interval [CI], -0.29 to 0.30; P=0.97), with no heterogeneity (I2=0%). There was also no difference in the VAS scores between the LR-PRP and control groups (SMD, -0.19; 95% CI, -0.57 to 0.20; P=0.34), with substantial heterogeneity (I2=56.7%). Regarding long-term follow-up, there was no difference in the VAS scores between the LP-PRP and control groups (SMD, -0.73; 95% CI, -1.69 to 0.23; P=0.134) with substantial heterogeneity (I2=88.4%). The LR-PRP group had lower VAS scores than the control group (SMD, -1.06; 95% CI, -2.02 to -0.09; P=0.032) with substantial heterogeneity (I2=92%). In the LP-PRP group, there was no significant difference in the success rate (odds ratio, 1.08; 95% CI, 0.07-16.47; P=0.956) with substantial heterogeneity (I2=87.7%). In the LR-PRP group, however, the patients who received PRP had a higher success rate than those in the control group (odds ratio, 2.85; 95% CI, 1.67-4.85; P<0.01) with substantial heterogeneity (I2=82.9%). LR-PRP may provide pain relief and successful outcomes for patients with LE compared with alternative local injections. Better results were observed with the use of LR-PRP than with the use of LP-PRP.

The Effect of Calcium Gluconate on Platelet Rich Plasma Activation for VEGF-A Expression of Human Dental Pulp Stem Cells.

Objective Platelet-rich plasma (PRP) activation is an important factor in triggering the initial release of blood-derived growth factors from platelets. Vascular endothelial growth factor-A (VEGF-A) can be expressed by human dental pulp stem cells (hDPSCs) and plays an important role in dental pulp angiogenesis. The aim of this study is to analyze the effects of calcium gluconate on PRP activation in hDPSC VEGF-A expression. Materials and Methods Two types of PRP and their corresponding activators were analyzed in this study: PRP (activated using calcium chloride/CaCl 2 ) and PRP-T (activated using CaCl 2 with the addition of 10% calcium gluconate). hDPSCs were obtained by using an out-growth method (DPSCs-OG), and harvest between the fifth and sixth passages, then cultured in three different media groups: control, PRP, and PRP-T, which were planted in 96 wells (5 × 10 3 each well). The VEGF-A expression of hDPSCs was analyzed by using an ELISA test and observed at 24, 48, and 72 hours. Statistical Analysis This study was performed by using one-way ANOVA ( p < 0.05) test. Results There were significant differences between all groups ( p < 0.05) at 48 and 72 hours of observations, and no significant differences in the PRP and PRP-T groups at 48 and 72 hours of observations ( p > 0.05). Conclusion PRP and PRP-T were equally effective in inducing VEGF-A expression of hDPSCs.

Regenerative Potential of Blood-Derived Products in 3D Osteoarthritic Chondrocyte Culture System.

Intra-articular injection of different types of blood-derived products is gaining popularity and clinical importance in the treatment of degenerative cartilage disorders such as osteoarthritis. The regenerative potential of two types of platelet-rich plasma (PRP), prepared in the presence of EDTA (EPRP) and citrate (CPRP) and an alternative blood product-hyperacute serum (hypACT) was evaluated using a 3D osteoarthritic chondrocyte pellet model by assessing the metabolic cell activity, cartilage-related gene expression and extracellular matrix deposition within the pellets. Chondrocyte viability was determined by XTT assay and it revealed no significant difference in metabolic activity of OA chondrocyte pellets after supplementation with different blood products. Nevertheless, the selection of blood products influenced the cartilage-related genes expression, ECM morphology and the tissue quality of pellets. Both PRP types had a different biological effect depending upon concentration and even though CPRP is widely used in clinics our assessment did not reveal good results in gene expression either tissue quality. HypACT supplementation resulted in superior cartilage-related genes expression together with tissue quality and seemed to be the most stable product since no remarkable changes were observed between the two different concentrations. All in all, for successful regenerative therapy, possible molecular mechanisms induced by blood-derived products should be always carefully investigated and adapted to the specific medical indications.

Adverse Reactions and Clinical Outcomes for Leukocyte-Poor Versus Leukocyte-Rich Platelet-Rich Plasma in Knee Osteoarthritis: A Systematic Review and Meta-analysis.

Background:Platelet-rich plasma (PRP) has gained attention as a therapeutic option for knee osteoarthritis; however, its efficacy varies widely. Leukocytes in PRP raise the concern of aggravating proinflammatory activity. To date, PRP has rarely been investigated with regard to leukocyte concentration.Purpose:To provide clinical evidence of the intra-articular injection of PRPs containing different leukocyte concentrations.Study Design:Systematic review; Level of evidence, 4.Methods:We systematically searched the MEDLINE, Embase, Cochrane Library, CINAHL, and Scopus databases. PRP was classified into leukocyte-poor (LP-PRP) and leukocyte-rich (LR-PRP). Clinical outcomes including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain score, International Knee Documentation Committee (IKDC) subjective score, and adverse reactions were evaluated. The Methodological Index for Non-Randomized Studies criteria were used for quality assessment.Results:Included were 32 studies with an evidence level between 1 and 4. Both LP-PRP and LR-PRP showed improvements above the minimal clinically important difference (MCID) in VAS pain score. No significant intergroup difference was seen at 3, 6, or 12 months of follow-up. Regarding function, both LP-PRP and LR-PRP showed improvements above the MCID in the WOMAC and IKDC scores, with no significant difference between the groups. Adverse reactions for pain were significantly higher in LR-PRP than in LP-PRP (odds ratio, 1.64; 95% confidence interval, 1.29-2.10; P = .01). After intra-articular PRP injection, LR-PRP showed a significantly higher rate of swelling than LP-PRP (odds ratio, 1.56; 95% confidence interval, 1.22-1.99; P = .02). The mean Methodological Index for Non-Randomized Studies score of the included studies was 18.6 (range, 10-24).Conclusion:Intra-articular PRP injection resulted in improvements above the MCID in terms of pain and function in patients with knee osteoarthritis up to 12 months. The risk of local adverse reactions appeared to be increased after LR-PRP compared with LP-PRP injection. The findings of this review can support the potential use of intra-articular PRP injection for the treatment of knee osteoarthritis. In clinical application, clinicians need to consider selecting a specific type of PRP for knee osteoarthritis.

Autologous Protein Solution Effect on Chondrogenic Differentiation of Mesenchymal Stem Cells from Adipose Tissue and Bone Marrow in an Osteoarthritic Environment.

Osteoarthritis (OA) is an inflammatory and degenerative disease, and the numerous treatments currently used are not fully effective. Mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) are proposed for OA treatment as biologic therapies. The aim of the study was to observe the role of autologous protein solution (APS), a type of PRP, on chondrogenic differentiation of 2 types of MSCs, from bone marrow (BMSCs) and adipose tissue (ADSCs), in an in vitro osteoarthritic microenvironment. Inflammatory culture conditions, mimicking OA, were obtained by adding interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα), or synovial fluid from patient osteoarthritic knees (OSF), to the culture medium. MSCs were then treated with APS. After 1 month of culture, both cell types formed mature micromasses, partially altered in the presence of IL-1β and TNFα but quite preserved with OSF. Inflammatory conditions hindered differentiation in terms of gene expression, not counterbalanced by APS. APS triggered type I collagen deposition and above all contributed to decrease the expression of metalloproteinases in the most aggressive conditions (IL-1β and TNFα in the culture medium). ADSCs originated micromasses more mature and less prone toward osteogenic lineage than BMSCs, thus showing to better adapt in an aggressive environment than BMSC. APS seems to act better on inflammation front and, between cell types, ADSCs respond better to the inflammatory microenvironment of OA and to the treatment with APS than BMSCs.

Clinical Efficacy of Platelet-Rich Plasma Injection and Its Association With Growth Factors in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized Double-Blind Controlled Clinical Trial As Compared With Hyaluronic Acid

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).

Characteristics of autologous protein solution and leucocyte-poor platelet-rich plasma for the treatment of osteoarthritis of the knee

Recently, platelet-rich plasma (PRP) has received attention as a treatment for patients with osteoarthritis of the knee (OAK), a chronic degenerative disease, to bridge the gap between conservative and surgical treatments. Here, we investigated the differences in the humoral factors present in two types of PRP purified using the Autologous Protein Solution (APS) kit (group Z; leucocyte-rich PRP) or the Cellaid Serum Collection Set P type (group J; leucocyte-poor [LP]-PRP). Differences in humoral factors between healthy subjects (n = 10) and OAK patients (n = 12; group Z = 6, group J = 6), and the relationship between humoral factors and clinical outcome scores were investigated. Both anti-inflammatory and inflammatory cytokines were highly enriched in APS. The concentrations of tumour necrosis factor (TNF)-α, platelet-derived growth factor, fibroblast growth factor, soluble TNF-receptor 2, soluble Fas and transforming growth factor-β1 were higher in group Z, while the total amounts were higher in group J. The concentration of interleukin-1 receptor antagonist was positively correlated with the magnitude of change in the clinical outcome score and may contribute to improving knee-joint function. This is the first description of the humoral factors in APS and LP-PRP prepared from healthy subjects or OAK patients of Asian descent.

Intra-articular injections of platelet-rich plasma in symptomatic knee osteoarthritis: a consensus statement from French-speaking experts

PurposeThere has been much debate regarding the use of intra-articular injections of platelet-rich plasma (PRP) as symptomatic treatment for knee osteoarthritis. The objective of this consensus was to develop guidelines for PRP injections in knee osteoarthritis according to the French National Authority for Health recommendations.MethodsFifteen physicians from different French-speaking countries (10 rheumatologists, 4 specialists in rehabilitation and sports medicine and 1 radiologist) were selected for their expertise in the areas of PRP and osteoarthritis. A comprehensive literature review was conducted on Medline including all published therapeutic trials, open studies, meta-analysis and systematic reviews focusing on the effects of PRP in knee OA, as well as fundamental studies concerning the characteristics of the various types of PRP and their mechanisms, indexed before April 2019. Using the method recommended by the French National Authority for Health inspired by the Delphi consensus process, 25 recommendations were finally retained and evaluated. The recommendations were classified as appropriate or not appropriate, with strong or relative agreement, or uncertain if a consensus was not achieved.ResultsAmong the 25 recommendations selected, the main ones are the following: (1) Intra-articular injections of PRP are an effective symptomatic treatment for early to moderate knee osteoarthritis. This recommendation was considered appropriate with a relative agreement (Median = 8; rank = 6–9). Level of evidence 1A. (2) A PRP treatment sequence in knee osteoarthritis may include 1–3 injections. This recommendation was considered appropriate with a strong agreement (Median = 9; rank = 7–9). Level of evidence 1A. (3) Leucocytes-poor PRP should be preferred in knee osteoarthritis. This recommendation was considered appropriate with a relative agreement (Median = 8; rank = 5–9). Level of evidence 5. (4) Intra-articular PRP knee injections should be performed under ultrasound or fluoroscopic guidance. This recommendation was considered uncertain with no consensus (Median = 8; rank = 3–9). Level of evidence 5. (5) PRP should not be mixed with an anesthetic or intra-articular corticosteroid. This recommendation was considered appropriate with a relative agreement (Median = 9; rank = 6–9). Level of evidence 5ConclusionThose 25 recommendations should standardize and facilitate the use of IA PRP injections, which are considered by experts as an effective treatment especially in early or moderate knee OA. Although a strong or relative agreement from the experts was obtained for most of the recommendations, many of them had a very low level of evidence (Level 5) and were principally based on the clinical experience of the experts.

Platelet-rich plasma promotes recruitment of macrophages in the process of tendon healing.

IntroductionResearchers have investigated the use of platelet-rich plasma (PRP) therapy. However, the mechanisms through which PRP affects tissue repair remain unclear. We hypothesize that PRP promotes tissue repair through not only via direct manner on the local cells but also via indirect manner that encourage the recruitment of reparative cells such as macrophages (MPs), and it depends on the quality of PRP including the concentration of leukocytes. The aim of this study is to elucidate the actions of the MPs in the mechanisms of PRP on tissue repair processes.MethodsLeukocyte-rich (LR) PRP and leukocyte-poor (LP) PRP were prepared from 12-week-old C57BL6 mice. Full-thickness defects were created in central third of patellar tendons of 12-week-old C57BL/6 mice for histologic analysis (n = 36) and 12-week-old B6.129P-Cx3cr1tm1Litt/J mice for flow cytometry analysis (n = 108). B6.129P-Cx3cr1tm1Litt/J mouse is GFP-positive only in the MP-linage cells thus MPs recruited to the repair tissue can be distinguished whether it had originated from administrated PRP or recruited from host mouse. Mice were treated either with LR-PRP, LP-PRP, or without PRP (control group). Histological analyses were performed to evaluate the tendon healing using Bonar score as semi-quantitative histological scoring system. Flow cytometric analyses were performed to count the number of GFP-positive cells around repaired patellar tendon. In addition, the ratio of pro-inflammatory MPs (M1)/anti-inflammatory MPs (M2) were analyzed in those GFP-positive cells. The statistical analysis was performed using GraphPad Prism ver6. P values < 0.05 were considered statistically significant.ResultsIn LR-PRP and LP-PRP groups, all variables in Bonar score such as cell morphology, cellularity, vascularity, and collagen arrangement were significantly improved in comparison with control group, indicating that both PRPs promote tendon hearing. LP-PRP promoted the tendon healing significantly faster than that of LR-PRP on postoperative day 28 (P < 0.001). LR-PRP enhanced angiogenesis (vascularity: P < 0.001), while LP-PRP improved the collagen arrangement on postoperative day 28 (collagen arrangement: P < 0.01). In other variables such as cell morphology and cellularity score, there were no significant differences between LR-PRP and LP-PRP groups in any time points. Flow cytometric findings showed that recruitment of GFP-positive MPs in the LR and LP-PRP groups were significantly increased from postoperative day 4 compared with control group without PRP treatment (P < 0.001). The majority of GFP-positive MPs were M1 at the initiation of tendon healing phase, and M2 were gradually increased from postoperative day 4. The number of M1 was significantly high both in the LP- and LR-PRP groups (day 4 and 7, p < 0.001), but the number of M2 was high only in the LP-PRP group (day 7 and 14, P < 0.05) when it compared with control group. The M1/M2 ratio on postoperative day 7 was significantly lower in the LP-PRP group than those in the control group (P < 0.05).ConclusionsThis study demonstrated that PRP enhanced the tendon healing and promoted the recruitment of MPs to the injured tissue. The subtypes of MPs were different depends on the types of PRPs, suggesting that leukocytes in PRP influence the effect of PRP therapy.

Quality comparison between two different types of platelet-rich plasma for knee osteoarthritis.

Introduction: Knee osteoarthritis (KOA), the most common form of osteoarthritis (OA) is a considerable health concern worldwide. Platelet-rich plasma (PRP) is a common therapeutic option for KOA. Different types of PRPs have varying efficacies. However, a comparative analysis of the qualities of these PRPs is lacking. Methods: Two types of PRPs, including autologous protein solution (APS), and leukocyte-poor PRP (LP-PRP) along with whole blood (WB) and platelet-poor plasma (PPP) were characterized for platelet content, leukocyte content, and composition in 10 healthy volunteers (HV) (the controlled laboratory study) and 16 KOA patients (a retrospective observational study). Additionally, the levels of the platelet-derived growth factor (PDGF)-BB, and different cytokines were estimated in HV. Results: In HV, the concentrations of platelets and leukocytes, levels of different cytokines, including interleukin 1 receptor antagonist (IL-1Ra), soluble TNF receptor type II (sTNF-RII), and IL-1β, and the ratio of IL-1Ra/IL-1β were significantly higher in APS, whereas the PDGF-BB was higher in LP-PRP than APS. In KOA patients, a higher concentration of platelets was observed in LP-PRP, and a higher concentration of leukocytes was observed in APS than LP-PRP. Following the PAW classification system, LP-PRP was classified as P2-B type in HV (51.3 × 104/μl) and KOA (53.4 × 104/μl), whereas APS was classified as P3-A type in HV (110.1 × 104/μl) and P2-A type in KOA (29.0 × 104/μl). In a retrospective observational study, the KOA patients who underwent APS injection had a higher incidence of arthralgia, and this arthralgia lasted for a longer time than LP-PRP injection in the same individual. Discussion: The quality of the two PRPs differed distinctively depending on their preparation methods, which might affect their clinical efficacies and adverse events. Therefore, the characterization of these parameters should be prioritized while choosing PRP.

The Effect of Blood-Derived Products on the Chondrogenic and Osteogenic Differentiation Potential of Adipose-Derived Mesenchymal Stem Cells Originated from Three Different Locations.

Background Adipose-derived mesenchymal stem cells (AD-MSCs) from fat tissue considered “surgical waste” during joint surgery may provide a potent source for regenerative medicine. Intra-articular, homologous fat tissue (Hoffa's fat pad, pouch fat) might possess a superior chondrogenic and osteogenic differentiation potential in comparison to extra-articular, nonhomologous fat. Blood products might further enhance this potential. Methods AD-MSCs were isolated from fat tissue of 3 donors from 3 locations each, during total knee replacement. Isolated cells were analyzed via flow cytometry. Cells were supplemented with blood products: two types of platelet-rich plasma (EPRP—PRP prepared in the presence of EDTA; CPRP—PRP prepared in the presence of citrate), hyperacute serum (hypACT), and standard fetal calf serum (FCS) as a positive control. The viability of the cells was determined by XTT assay, and the progress of differentiation was tested via histological staining and monitoring of specific gene expression. Results Blood products enhance ex vivo cell metabolism. Chondrogenesis is enhanced by EDTA-PRP and osteogenesis by citrate PRP, whereas hyperacute serum enhances both differentiations comparably. This finding was consistent in histological analysis as well as in gene expression. Lower blood product concentrations and shorter differentiation periods lead to superior histological results for chondrogenesis. Both PRP types had a different biological effect depending upon concentration, whereas hyperacute serum seemed to have a more consistent effect, independent of the used concentration. Conclusion (i) Blood product preparation method, (ii) type of anticoagulant, (iii) differentiation time, and (iv) blood product concentration have a significant influence on stem cell viability and the differentiation potential, favouring no use of anticoagulation, shorter differentiation time, and lower blood product concentrations. Cell-free blood products like hyperacute serum may be considered as an alternative supplementation in regenerative medicine, especially for stem cell therapies.