Leukocyte-poor Platelet-rich Plasma Research Articles

Morphofunctional characteristics of proliferation and apoptosis of germinal epithelium: pathogenesis of temporary azoospermia after local electron irradiation.

At present, the violation of male reproductive function caused by electron irradiation, leading to a decrease in the proliferative activity of germ cells, as well as the development of methods for its correction are relevant. The effect of leukocyte-poor platelet-rich plasma (LP-PRP) growth factors, which have a high regenerative capacity for the restoration of spermatogenesis, remains poorly understood. Objective of the study: immunohistochemical (IHC) assessment of the proliferation of germinal epithelium after electron irradiation with a dose of 2 Gy. Wistar rats (n=60) were divided into groups (conventional names): (I) control (n=30), which were injected with saline; (II) single local irradiation of the testes with electrons at a dose of 2 Gy (n=30). Animals were gradually withdrawn from the experiment over 11 weeks: 5 animals one week after irradiation, and then 5 animals once every 2 weeks. The testes were studied by histological and IHC methods using antibodies to Ki-67, Bcl-2, and p53. Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) method was used to study DNA fragmentation in germ cells, which were stained with TdT solution (Thermo Fisher, USA) and incubated for 60 minutes. The nuclei were counterstained with 4',6-diamidino-2-phenylindole (DAPI) (blue spectrum) (Thermo Fisher), and the luminescence intensity was controlled in a fluorescent microscope with a set of fluorescein isothiocyanate (FITC) filters (green spectrum). IHC analysis of testes after irradiation showed a shift in the proliferative-apoptotic balance towards apoptosis of germ cells: a decrease in the expression levels of Ki-67 (16.3%±1.1%, P<0.05) and Bcl-2 (9.1%±1.1%, P<0.05), an increase in p53-positive cells (74.8%±1.2%, P<0.05) by the end of the experiment. In the experimental model, local irradiation of the testes with electrons at a dose of 2 Gy causes the development of focal hypospermatogenesis, affecting up to 1/8 of the sections of the tubules (in the first week) with a subsequent increase to 1/4 (in the second month), with a tendency to recovery in the third month (temporary azoospermia). The basis of focal hypospermatogenesis is the irradiation-induced proliferative-apoptotic imbalance towards the dominance of apoptosis, which is most pronounced in the pool of spermatogonia.

Results of Treating Mild to Moderate Knee Osteoarthritis with Autologous Conditioned Adipose Tissue and Leukocyte-Poor Platelet-Rich Plasma.

Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Much progress has been made in regenerative medicine for the symptomatic treatment of KOA, including products containing stromal vascular fraction (SVF) and platelet-rich plasma (PRP). The aim of this study was to evaluate clinical and radiological findings after the application of autologous conditioned adipose tissue (ACA) and leukocyte-poor PRP (LP-PRP) in patients with mild to moderate KOA. A total of 16 patients (eight male and eight female) with changes related to KOA on the magnetic resonance imaging (MRI), but without severe osteophytosis, full-thickness cartilage loss, or subchondral bone involvement were included in this study. Patients received an intraarticular, ultrasound-guided injection of ACA and LP-PRP. Clinical scores, including a visual analog scale for pain (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were evaluated at baseline and at the three and six month follow-ups showing a statistically significant improvements at three and six months post-intervention. Furthermore, the delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) indices were evaluated at baseline and at the three and six month follow-ups showing no significant changes after treatment with ACA and LP-PRP, which were actually equal to the dGEMRIC indices measured in the control group (hyaluronic acid applied in contralateral knees without osteoarthritis). ACA with LP-PRP presents a viable minimally invasive therapeutic option for the clinical improvement of mild to moderate KOA. However, MFAT produced by different systems is likely to differ in cellular content, which can directly affect the paracrine effect (cytokine secretion) of mesenchymal stem cells and consequently the regeneration process.

Intra-Articular Leukocyte-Poor Platelet-Rich Plasma Injections for Japanese Patients With Osteoarthritis of the Knee: A Three-Year Observational Retrospective Study After Phase 1 and Phase 2a Trials.

We have previously confirmed the safety and feasibility of intra-articular (IA) platelet-rich plasma (PRP) injections in Japanese patients with osteoarthritis (OA) of the knee. This study aimed to investigate the clinical and radiological outcomes in patients who were followed up for three years. Nine patients were evaluated in this observational study. All the patients were women with a mean age of 60.6 years. PRP was prepared by single centrifugation and classified as leukocyte-poor (LP)-PRP, and was administered via three IA injections at weekly intervals. Patients were evaluated at baseline and final follow-up using the Kellgren-Lawrence (KL) grade and the Japanese Orthopedics Association (JOA) score. The need for additional treatment was also investigated at the final follow-up. At a mean follow-up of three years, the JOA score improved from 75 points (p) to 83.8 p. The sub-categorical scores changed as follows: gait, 23.1-26.9 p; stairs, 12.5-17.5 p; range of motion, 30-30 p; and swelling, 9.4-10 p. While the KL grade was maintained in six patients, it progressed in two patients from I to II and II to III, respectively. Two patients received additional treatment at the final follow-up. At the final follow-up, the functional knee score, especially gait and the ability to go up and down the stairs, improved in six out of eight patients without additional treatment. These results suggest that LP-PRP injections produced safe outcomes without OA-worsening in most patients at three-year follow-up.

Are leukocyte-poor or multiple injections of platelet-rich plasma more effective than hyaluronic acid for knee osteoarthritis? A systematic review and meta-analysis of randomized controlled trials.

Platelet-rich plasma (PRP) has gained popularity as a treatment option for knee osteoarthritis; however, its efficacy remains controversial. The optimal leukocyte concentration and number of injections have not been well investigated. This study was, therefore, designed to provide clinical evidence on the leukocyte concentration and number of intra-articular injections of PRP via a meta-analysis of randomized controlled trials (RCTs). The MEDLINE, Embase, Cochrane Library, CINAHL, and Scopus databases were searched and RCTs comparing PRP and hyaluronic acid (HA) for treating knee osteoarthritis were included. Clinical outcomes, including visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and adverse reactions, were evaluated. A total of 138 studies were screened, of which 21 level 1 RCTs (2086 knees; 1077 PRP and 1009 HA) were included. PRPs showed significant improvement in pain according to the VAS score compared to HA at 6 and 12months, regardless of leukocyte concentration. Both single and multiple injections of PRP improved pain better than HA at 12months. Regarding function, both single and multiple injections of leukocyte-poor PRP and leukocyte-rich PRP led to significantly better improvement in total WOMAC score compared with HA at 6months. There was no significant difference in procedure-related knee pain or swelling between the PRP and HA groups. Leukocyte-rich PRP had a significantly higher odds ratio for procedure-related knee pain or swelling compared to HA (odds ratio, 3.3 [95% confidence interval, 1.1-10.2], P = .037). Based on evidence from Level 1 studies, intra-articular injection of PRP improves pain and function in patients with knee osteoarthritis for up to 12months and is superior to HA, regardless of leukocyte concentration or number of injections. The findings of this study support the routine clinical use of intra-articular injections of PRP for the treatment of knee osteoarthritis, regardless of the type and frequency of PRP injection. Meta-analysis of level I studies.

Clinical Outcomes of Pectoralis Major Tendon Repair with and without Platelet-Rich Plasma

PurposeTo assess clinical outcomes following pectoralis major tendon (PMT) repairs and to compare outcomes of PMT repairs augmented with and without leukocyte-poor platelet-rich plasma (LP-PRP).MethodsA retrospective review of prospectively collected data was performed of patients who underwent a PMT repair from May 2007 to June 2019 with a minimum of 2-year follow-up. Exclusion criteria included revision PMT repair, PMT reconstruction, and concomitant repair of another glenohumeral tendon/ligament. LP-PRP was injected surrounding the PMT repair before wound closure. Patient-reported outcome (PRO) data were collected preoperatively and evaluated at final follow-up using the American Shoulder and Elbow Surgeons Score (ASES), Single Assessment Numeric Evaluation Score (SANE), Quick Disabilities of the Arm, Shoulder and Hand Score (QuickDASH), and Short Form 12 physical component summary (SF-12 PCS), patient satisfaction with outcomes.ResultsTwenty-three men (mean age, 38.6 years; range, 20.5-64.3 years) were included in the final analysis. Mean time from injury to surgery was 30 days (range, 3-123 days). Follow-up was obtained for 16 of 23 patients (70%) at a mean of 5.1 years (range 2.0-13.0 years). Significant improvement in PROs was observed (ASES: 59.0 → 92.4, P = .008; SANE: 44.4 → 85.9, P = .018; QuickDASH: 44.4 → 8.5, P = .018; and SF-12 PCS: 42.5 → 52.6, P = .008). Median satisfaction was 9 of 10 (range, 6-10). Patients receiving LP-PRP had superior ASES (99.6 vs 83.0, P = .001), SANE (94.8 vs 74.6, P = .005), QuickDASH (0.24 vs 19.1, P = .001), and patient satisfaction (10 vs 9, P = .037) scores compared with those without PRP. PROs were unchanged based on chronicity, mechanism of injury, or tear location. One patient had revision surgery at 3.4 years due to adhesions.ConclusionsPMT repair produces improved PROs at final follow-up when compared with preoperative values.Level of EvidenceLevel III, retrospective comparative therapeutic trial.

Autologous microfragmented adipose tissue and leukocyte-poor platelet-rich plasma combined with hyaluronic acid show comparable clinical outcomes for symptomatic early knee osteoarthritis over a two-year follow-up period: a prospective randomized clinical trial

PurposeThe purpose of this prospective randomized clinical trial is to compare the clinical outcomes of three injections of leucocyte-poor platelet-rich plasma (LP-PRP) and hyaluronic acid (HA) to a single dose of autologous microfragmented adipose tissue (AMAT) in patients with mild osteoarthritis at a two-year follow-up.MethodsEighty symptomatic knees in fifty patients (mean age: 62.38 ± 11.88 years) with Kellgren-Lawrence grade 0 to 2 osteoarthritis were non blinded, randomly allocated into two equal groups. Group 1 consisted of 40 knees that received autologous LP-PRP + HA; Group 2 consisted of 40 knees treated with a single dose of AMAT injection. The outcomes were measured by Tegner, Marx, Visual Analogue Scale (VAS) for pain, International Knee Documentation Committee, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 6 (T1), 12 (T2), and 24 (T3) months. Adverse events were recorded at each follow-up timepoint. To assess score differences among subjects of the same gender and age, a subgroup analysis was performed.ResultsBoth groups had significant clinical and functional improvement at 6, 12, and 24 months (p < 0.05). Comparing the two groups, the AMAT groups showed significantly higher pre-operative Marx score (3.35 ± 4.91 vs. 1.78 ± 3.91) and VAS score (5.03 ± 2.02 vs. 3.85 ± 1.68) (p < 0.05), higher VAS (3.89 ± 2.51 vs. 2.64 ± 2.00) at T2 and KOOS-ADL (79.60 ± 20.20 vs. 65.68 ± 23.62), and lower KOOS-Sports (50.30 ± 30.15 vs. 68.35 ± 30.39) at T3 (p < 0.05). No patient from either group had experienced major adverse effects. In the LP-PRP group 12 (30%) patients presented swelling, redness, and mild pain for one day after injection and two patients had synovitis for two days and required paracetamol and local ice. In AMAT group 5 (12.5%) patients had ecchymosis and bruising at the fat aspiration site for three days.ConclusionAMAT did not show significant superior clinical improvement compared with three LP-PRP combined with HA injections in terms of functional improvement at different follow-up points. Both procedures were safe with no major complications reporting good results at mid-term follow-up, improving knee function, pain, and quality of live regardless of age and gender.Level of evidenceLevel I—Prospective Randomized Clinical Trial.

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.

Paper 14: Leukocyte-Poor Platelet Rich Plasma versus Leukocyte-Poor Platelet Rich Plasma Plus Hyaluronic Acid for the Treatment of Symptomatic Knee Osteoarthritis: A Prospective, Randomized Control Trial with 2 Year Follow Up

Objectives:The main objective of this study was to determine if hyaluronic acid (HA) injected at the same time as leukocyte-poor platelet rich plasma LP-PRP would improve the performance compared to LP-PRP alone in the treatment of symptomatic knee osteoarthritis. We hypothesized that the addition of hyaluronic acid would improve the efficacy of LP-PRP.Methods:Patients between the ages of 30 and 80 who had symptomatic Kellgren-Lawrence grades 1-4 were eligible for the study. Patients were offered enrollment and screened with inclusion and exclusion criteria. The participants were randomized into two study groups and scheduled to receive a three-injection series. Group 1 [LP-PRP] received 3 intra-articularinjections of LP-PRP dosed at one week intervals. Group 2 [LP-PRP/HA] received 3 intra-articular injections of LP-PRP dosed at one week intervals, with hyaluronic acid (Hymovis) injected concomitantly for the first two injections. The Arthrex Autologous Conditioned Plasma system was used to prepare all LP-PRP injections. Participants were blinded to injection randomization and wore a blind fold for the first two injections. Participants completed patient reported outcome questionnaires prior to their injections and at 1, 3, 6, 12, 18, and 24 months after the final injection. The questionnaires included the Western Ontario and McMaster Universitys Osteoarthritis Index (WOMAC), International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS).Results:The study population included 63 total subjects, 32 subjects were randomized to Group 1 (ACP) with average age 55.8 +/- 11.4, 31 subjects were randomized to group 2 (ACP+HA) with average age 60.4 +/- 9.0. Both groups demonstrated improvement over baseline at 1 and 3 months, with improvement plateauing at 3 months. Both groups demonstrated improvement over baseline out to 24 months. The LP-PRP/HA group demonstrated increased improvement compared to group 1 at 1 and 3 months but consistently trended down in both the WOMAC, IKDC, and KOOS scores however statistical significance was not reached. The LP-PRP groups improvement was consistent until the 18 month time point. Complete patient reported outcome data is included in Table 1. Change in WOMAC, IKDC and KOOS scores over time are represented in Figures 1, 2, and 3 respectively.Conclusions:Both groups demonstrated improvement over baseline at 1 and 3 months, with improvement plateauing at 3months. Both groups demonstrated improvement over baseline out to 24 months. The LP-PRP/HA group demonstrated increased improvement compared to the LP-PRP group at 1 and 3 months, however statistical significance was not reached and the improvement diminished after the 12 month time point. The LP-PRP group did not see a diminishing improvement until the 18 month time point.Figure 1.IKDCScore.Figure 2.WOMAC Score.Figure 3.KOOS Scores.

The Use of Intra-articular Platelet-Rich Plasma as a Therapeutic Intervention for Hip Osteoarthritis: A Systematic Review and Meta-analysis

Background: There is a cohort of patients in whom hip preservation surgery is not indicated, because they have developed signs of early osteoarthritis (OA), and nor can they have a hip replacement, as they are too early in the disease process. Management of this cohort of patients is not standardised and both pharmacological and nonpharmacological measures are utilised to reduce pain. Interventions available for early OA include intra-articular injections of steroids, viscosupplementation and more recently platelet-rich plasma (PRP). However, the use of PRP in hip OA has not yet been studied systematically. Purpose: To assess intra-articular PRP as a therapeutic intervention for hip OA, including the duration of efficacy, influence of dose and composition of PRP, and the incidence of adverse effects. Study Design: A systematic review and meta-analysis; Level of evidence, 4. Methods: We performed literature searches on the MEDLINE, EMBASE, CINAHL, WEB OF SCIENCE, COCHRANE, and SCOPUS databases, and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Data were pooled using random-effects meta-analysis. We assessed the quality of the included studies using the methodological index for non-randomized studies instrument, with an additional assessment for randomized controlled trials with the revised Cochrane risk of bias tool for randomized trials. This is the first study to concisely collate the available data on the use of PRP in hip OA. Results: Eight studies were included in the analysis, with data from a total of 331 patients. PRP significantly reduced pain compared with the baseline at multiple time points, with the greatest effect at the 1- to 2-month follow-up, but PRP significantly improved function only at the 1- to 2-month follow-up. A significantly larger reduction in pain was achieved with a single injection of PRP compared with multiple injections, a total injected dose of PRP <15 mL compared with ≥15 mL, and use of a leukocyte-poor PRP preparation compared with leukocyte-rich PRP. There were no lasting adverse effects. Conclusion: Low- and moderate-quality evidence suggests that PRP reduces pain and improves function at the end-point follow-up of studies compared with the baseline. Moderate-quality evidence suggests that a larger reduction in pain is achieved with a single injection of PRP compared with multiple injections, and low-quality evidence attributes a larger reduction of pain with a total injected dose of PRP <15 mL compared with ≥15 mL and using leukocyte-poor PRP compared with leukocyte-rich PRP.

Efficacy of a Novel Intra-Articular Administration of Platelet-Rich Plasma One-Week Prior to Hyaluronic Acid versus Platelet-Rich Plasma Alone in Knee Osteoarthritis: A Prospective, Randomized, Double-Blind, Controlled Trial.

Recent studies have suggested that the combined injection of platelet-rich plasma (PRP) and hyaluronic acid (HA) may have additive benefits for knee osteoarthritis over PRP alone, but there is insufficient evidence to support this combined injection. Moreover, the simultaneous injection of PRP and HA may offset the combined effect. Hence, the aim of this prospective, randomized, double-blind study was to assess their combined efficacy with a novel injection protocol. Forty-six study subjects with unilateral knee osteoarthritis were randomized to receive either a single-dose injection of HA (intervention group) or normal saline (control group) 1 week after a single-dose injection of leukocyte-poor PRP. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and static balance and the risk of falls measured by Biodex Balance System were, respectively, the primary and secondary outcome measures. Evaluations were performed at baseline, 1 month, 3 months, 6 months, and 12 months post-injection. The intervention group exhibited significant declines in WOMAC pain, stiffness, and total scores, as well as static balance, compared to the control group (p < 0.05). These randomized double-blind control trials, with novel protocol of intra-articular injection of PRP 1-week prior to HA, provide greater symptom relief and improve static balance compared to PRP alone in patients with knee osteoarthritis.

Leukocyte-rich and Leukocyte-poor Platelet-rich Plasma in Rotator Cuff Repair: A Meta-analysis

To systematically review of randomized controlled trials (RCTs) to compared the effects of leukocyte-rich and leukocyte-poor platelet-rich plasma in arthroscopic rotator cuff repair. Two independent reviewers comprehensively searched PubMed, Embase, and Cochrane library databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comparison of leukocyte-rich platelet-rich plasma or leukocyte-poor platelet-rich plasma in rotator cuff repair in a level I RCTs. Methodological quality assessment was carried out using Cochrane Review Manager 5.3 software. P<0.05 was considered statistically significant. Nine RCTs with 540 patients were included in this review. Meta-analysis showed that leukocyte-poor platelet-rich plasma in significantly reduced retear rate in rotator cuff repair [RR=0.56 95% CI (0.42, 0.75); P<0.05), and in clinical results, the constant score [MD=3.67, 95% CI (1.62, 5.73); P=0.0005], UCLA score [MD=1.60, 95% CI (0.79, 2.42); P=0.0001], ASES score [MD=2.16, 95% CI (0.12, 4.20); P=0.04] were significantly improved. There was a significant result in favor of PRP for the Constant score [MD=-1.24, 95% CI (-1.50, -0.99); P<0.00001], while SST scores were not significantly different among all groups [MD=0.21, 95% CI (-0.21, 0.64); P=0.32]. In conclusion, leukocyte-poor platelet-rich plasma can improved the clinical function and reduced retear rate in arthroscopic rotator cuff repair. In contrast, the efficacy of leukocyte-rich platelet-rich plasma was not significantly improved with the exception of VAS score.

Intra-Articular Injection of Platelet-Rich Plasma Is More Effective than Hyaluronic Acid or Steroid Injection in the Treatment of Mild to Moderate Knee Osteoarthritis: A Prospective, Randomized, Triple-Parallel Clinical Trial.

Purpose: To prospectively compare the efficacy and safety of intra-articular injections of platelet-rich plasma (PRP) with hyaluronic acid (HA) and glucocorticosteroid (CS) control groups for knee osteoarthritis (KOA) in a randomized, triple-parallel, single-center clinical trial. Methods: A total of 75 patients were randomly assigned to one of three groups receiving a single injection of either leukocyte-poor platelet-rich plasma (25 knees), hyaluronic acid (25 knees), or glucocorticosteroid (25 knees). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was collected at baseline and 6, 12, and 26 weeks after treatment. Results: After 6 weeks of PRP administration, a decrease in the mean WOMAC value was observed in all three study groups. Three months after administration, the greatest decrease in the mean WOMAC value was obtained in the PRP group. The results in the HA and CS groups were similar (p = 0.681). In the one-way analysis of variance and post hoc analysis using the HSD Tukey test, a significantly greater improvement was shown by comparing the PRP and CS groups (p = 0.001), and the PRP and HA groups (p = 0.010). After intra-articular injection of CS, the reduction in pain was greatest 6 weeks after administration, and the mean value was the lowest among all groups. During subsequent visits, the value of the pain subscale increased, and after 6 months, it was the highest among the studied groups. Using the Wilcoxon paired test, no PRP effect was found to reduce stiffness at the 6-month follow-up (p = 0.908). Functional improvement was achieved in all groups, i.e., a decrease in the value of this subscale 6 months after administration. The largest decrease was seen in the group that received PRP (p < 0.001) and then in the HA group. The smallest decrease among the investigated methods was shown in the CS group. Conclusions: Intra-articular injections of PRP can provide clinically significant functional improvement for at least 6 months in patients with mild to moderate KOA which is superior to HA or CS injections.

Effectiveness of Platelet-Rich Plasma for Lateral Epicondylitis: A Systematic Review and Meta-analysis Based on Achievement of Minimal Clinically Important Difference.

Background:The effectiveness of platelet-rich plasma (PRP) injection in the treatment of lateral epicondylitis remains debatable.Purpose:To evaluate the effectiveness of PRP in lateral epicondylitis treatment using minimal clinically important difference (MCID) values as a reference and to investigate if leukocyte content can influence the effectiveness of the therapy.Study Design:Systematic review; Level of evidence, 4.Methods:Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the authors searched the Medline and Scopus databases for studies on lateral epicondylitis and PRP therapy that used the following patient-reported outcome measures (PROMs): visual analog scale (VAS) for pain; Disabilities of the Arm, Shoulder and Hand (DASH); Patient-Rated Tennis Elbow Evaluation (PRTEE); and Mayo Clinic Performance Index (MAYO). The weighted arithmetic means for the PROMs were calculated at baseline (week 0) and follow-up weeks 4, 8, 12, 24, 52, and 104. The mean differences in outcomes (ΔVAS, ΔDASH, ΔPRTEE, and ΔMAYO) were compared with the MCID values at each follow-up point. In addition, the effectiveness of leukocyte-rich PRP (LR-PRP) versus leukocyte-poor PRP (LP-PRP) was also compared. The Student t test was used in all analyses.Results:A total of 26 studies were included in the analysis. After PRP injection, all PROM scores improved with time. The scores improved significantly from baseline to each follow-up time (P < .0001), with the exception of the PRTEE (no significant difference at follow-up weeks 12 and 52). The mean difference in scores from baseline exceeded the respective MCIDs from weeks 4 to 104 for the VAS and DASH, from weeks 4 to 52 for the MAYO, and from weeks 8 to 52 for the PRTEE. The MCID for each of the PROMs was exceeded at almost every observation period in both the LR-PRP and the LP-PRP systems.Conclusion:Based on comparisons with the MCID values of commonly used outcome scores, PRP seems to be an effective form of treatment for lateral epicondylitis. Both the LR- PRP and the LP- PRP systems were effective in the context of meeting the MCID.

An experimental approach to comprehend the influence of platelet rich growth factors on spermatogenesis

Leukocyte-poor platelet-rich plasma (LP-PRP) has a potential influence on tissue regeneration by stimulating the proliferation and differentiation of progenitor cells. The aim of this work is the morphological assessment of spermatogenesis under the influence of growth factors after electron irradiation. Materials and methods Experimental animals (n = 135) were divided into 5 groups: I – control (n = 10); II – 2IR (n = 35; 2 Gy); III – 2IR + LP-PRP + IGF-1 (n = 30); IV – 2IR + LP-PRP (n = 30); V – LP-PRP (n = 30). Results Electron irradiation reduces the number of germ cells in comparison with the control group. After injection of LP-PRP + rhIGF-1 significantly increased the number of germ cells, Sertoli and Leydig cells, the height of germinal epithelium, area and diameter of seminiferous tubules. Conclusion LP-PRP + rhIGF-1 has a normalizing effect on structural and functional disorders of the testis caused by electron irradiation.

Effects of leukocyte-rich platelet-rich plasma and leukocyte-poor platelet-rich plasma on the healing of bone-tendon interface of rotator cuff in a mice model

Platelet-rich plasma (PRP) is widely used clinically to treat tendon injuries, and often contains leukocytes. However, the debate regarding the concentration of leukocytes in PRP is still ongoing. This study aimed to evaluate the therapeutic effects of leukocyte-rich platelet-rich plasma (LR-PRP) and leukocyte-poor platelet-rich plasma (LP-PRP) on the healing of the bone-tendon interface (BTI) of the rotator cuff. A total of 102 C57BL/6 mice were used. Thirty mice were used to prepare the PRP, while 72 underwent acute supraspinatus tendon injury repair. The animals were then randomly assigned to three groups: LR-PRP, LP-PRP and control groups. The mice were euthanized at 4 and 8 weeks postoperatively, and histological, immunological and biomechanical analyses were performed. The histological results showed that the fusion effect at the bone-tendon interface at 4 and 8 weeks after surgery was greater in the PRP groups and significantly increased at 4 weeks; however, at 8 weeks, the area of the fibrocartilage layer in the LP-PRP group increased significantly. M2 macrophages were observed at the repaired insertion for all the groups at 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the control group, but some M2 macrophages were retained at the repaired site in the LR-PRP and LP-PRP groups. Enzyme-linked immunoassay results showed that the concentrations of IL-1β and TNF-α in the LR-PRP group were significantly higher than those in the other groups at 4 and 8 weeks, while the concentrations of IL-1β and TNF-α in the LP-PRP group were significantly lower than those in the control group. The biomechanical properties of the BTI were significantly improved in the PRP group. Significantly higher failure load and ultimate strength were seen in the LR-PRP and LP-PRP groups than in the control group at 4 and 8 weeks postoperatively. Thus, LR-RPR can effectively enhance the early stage of bone-tendon interface healing after rotator cuff repair, and LP-PRP could enhance the later stages of healing after rotator cuff injury.

Injection of Leukocyte-Poor Platelet-Rich Plasma for Moderate-to-Large Rotator Cuff Tears Does Not Improve Clinical Outcomes but Reduces Retear Rates and Fatty Infiltration: A Prospective, Single-Blinded Randomized Study

To determine whether leukocyte-poor platelet-rich plasma (Lp-PRP) reduced retear rates, reduced fatty infiltration, and improved functional outcomes in patients with degenerative moderate-to-large rotator cuff tears. This was a randomized controlled study at a single center. A consecutive series of 104 patients with moderate-to-large rotator cuff tears was enrolled and randomly allocated to a control group (double-row suture-bridge arthroscopic rotator cuff repair alone, n= 52) and a study group (double-row suture-bridge repair followed by 3 Lp-PRP injections at the tendon repair site during surgery, at days 7 and 14 after surgery, n= 52). All patients were followed up for 27.2 months (range 24-36 months), with University of California at Los Angeles (UCLA) shoulder rating scale, the Constant score, and a visual analog scale (VAS) evaluated respectively. The integrity and fatty infiltration of repaired tissue were assessed by magnetic resonance imaging using the Sugaya classification and Goutallier grade classification at 24 months after surgery. Statistical analysis was performed based on the t test, χ2 test, and the Kendall tau-b correlation coefficient. Four patients refused follow-up, and 11 patients had incomplete data. Eventually, a total of 89 patients were available for 24 months follow-up. The mean UCLA score increased from 14.80 ± 2.53 to 29.37 ± 2.06 in control group and from 13.74 ± 3.30 to 30.14 ± 2.32 in study group (P= .103). The mean Constant score increased from 46.56 ± 5.90 to 86.83 ± 4.94 in control group and from 44.37 ± 7.92 to 88.80 ± 4.92 in study group (P= .063). The VAS score decreased from 3.22 ± 1.24 to 0.97 ± 1.12 in control group and in 3.49 ± 1.52 to 1.16 ± 0.99 in study group (P= .41). All differences in UCLA score, Constant score, and VAS between pre- and postoperation achieved minimal clinically important differences proposed for arthroscopic rotator cuff repair. Of the 89 patients, 76 had magnetic resonance imaging performed at 24 months after surgery. The retear rate was 17.6% in study group, which was lower than that in control group (38.1%, P= .049). In addition, the Goutallier grade was found to be significant difference between groups postoperatively (Kendall tau-b -0.24, P= .03) but no significant difference preoperatively (Kendall tau-b -0.18, P= .11). There were no complications in the patients. Our procedures involving repeated injections of Lp-PRP during surgery and at days 7 and 14, as described in this study, have positive effects on reducing retear rate and promoting Goutallier grade in patients following arthroscopic rotator cuff repair and could also provide substantial clinical outcomes that reach the minimal clinically important difference for surgical treatment. However, given the numbers available for analysis, it did not promote better clinical results when compared with the control group. II, randomized controlled study.

Leukocyte-Rich Platelet-Rich Plasma Has Better Stimulating Effects on Tenocyte Proliferation Compared With Leukocyte-Poor Platelet-Rich Plasma.

Background:Rotator cuff (RC) tendinopathy is one of the most common causes of shoulder pain. Platelet-rich plasma (PRP) has been frequently used in clinical scenarios, but its efficacy remains inconsistent.Purpose:To investigate the different responses of human tenocytes from torn RCs to leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) in a 2-chamber coculture device.Study Design:Controlled laboratory study.Methods:PRP was prepared using different platelet and leukocyte concentrations according to 5 groups: (1) LR-PRP with 5000 platelets/µL, (2) LR-PRP with 10,000 platelets/µL, (3) LP-PRP with 5000 platelets/µL, (4) LP-PRP with 10,000 platelets/µL, and (5) control with only culture medium supplementation and without PRP stimulation. Platelet-derived growth factor–AB (PDGF-AB) and transforming growth factor–β1 (TGF-β1) were measured in LR-PRP and LP-PRP via enzyme-linked immunosorbent assay. Microscopy, water-soluble tetrazolium salt assay, and quantitative real-time polymerase chain reaction were used to investigate the morphology, proliferation, and gene expression of RC tenocytes exposed to different PRP formulations. Data were collected from at least 3 independent measurements. The results were analyzed via 1-way analysis of variance, followed by the post hoc Bonferroni test.Results:The ratio of leukocytes to 5000 platelets/µL was 29.5 times higher in LR-PRP than in LP-PRP (P < .05). In the 5000 platelets/µL groups, the levels of TGF-β1 and PDGF-AB were both significantly higher in LR-PRP versus LP-PRP (TGF-β1: 367.0 ± 16.5 vs 308.6 ± 30.3 pg/mL, respectively [P = .043]; PDGF-AB: 172.1 ± 1.8 vs 94.1 ± 4.2 pg/mL, respectively [P < .001]). Compared with the control group, RC tenocyte proliferation was 1.42 ± 0.01 and 1.41 ± 0.03 times higher in the LR-PRP groups with 5000 platelets/µL and 10,000 platelets/µL, respectively (P < .05). The expression of tenocyte-related genes was higher in tenocytes cultured in LR-PRP.Conclusion:Both the LR-PRP groups with 5000 platelets/µL and 10,000 platelets/µL induced more growth factor release and increased RC tenocyte proliferation than did the LP-PRP groups.Clinical Relevance:In RC repair, LR-PRP may be better than LP-PRP for increasing the proliferation of tenocytes.

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.

Clinical Response After Treatment of Knee Osteoarthritis With a Standardized, Closed-System, Low-Cost Platelet-Rich Plasma Product: 1-Year Outcomes.

Background:Intra-articular infiltration of platelet-rich plasma (PRP) is an alternative therapeutic option to classic hyaluronic acid for the treatment of symptomatic knee osteoarthritis (KOA). However, variation in preparation methods and quality assessment of PRP makes the study of its real clinical efficacy difficult.Purpose:To (1) evaluate the clinical efficacy of a characterized PRP product prepared in a standardized manner and in a closed-system for the treatment of KOA and to (2) evaluate the association of the clinical response to PRP-related variables.Study Design:Case series; Level of evidence, 4.Methods:We recruited 130 patients with nonoperative KOA and evaluated them for 1 year. PRP was prepared from a donation of autologous blood, obtaining 3 aliquots of approximately 10mL of product, which were frozen, allowing platelet disruption, platelet factor release, and long-term storage, until administration. Patients were treated 3 consecutive times every 4 weeks with an intra-articular PRP knee injection under sterile conditions. Complete blood count was performed on the whole-blood sample and the processed PRP before freezing it, for product quality assessment. Patients were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and basic satisfaction scale at 3 months, 6 months, and 1 year after intervention.Results:Quality assessment confirmed a leukocyte-poor PRP product (white blood cell count, 0.09 ± 0.09 × 109/L) with a high platelet purity (platelet count, 630.86 ± 191.75 × 109/L). WOMAC scores improved, and basic satisfaction was achieved in 70% of patients. No adverse events were reported. No correlations were observed between PRP quality parameters and clinical results. PRP complete treatment production costs were €108/US$125 (€36/US$41.6 per injection).Conclusion:This standardized PRP production method resulted in improved WOMAC scores at 1 year postoperatively in 70% of patients with KOA. This technique was safe and affordable and ensured consecutive infiltrations with the same product to each patient.

Leukocyte-Rich versus Leukocyte-Poor Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Trial

Background: Platelet-rich plasma (PRP) is gaining large interest in clinical practice as a minimally invasive injective treatment for knee osteoarthritis (OA). Different preparation methods are available, and the presence of leukocytes, deemed detrimental in some preclinical studies, is one of the most debated aspects regarding PRP efficacy. Purpose: To compare the safety and effectiveness of leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) for the treatment of knee OA. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 192 patients with symptomatic knee OA (Kellgren-Lawrence grade 1-3) were randomly allocated to 3 weekly injections of LR-PRP or LP-PRP. LP-PRP was obtained with a filter for leukodepletion. LR-PRP and LP-PRP were divided into aliquots of 5 mL, with a mean platelet concentration of 1146.8 × 109/L and 1074.9 × 109/L and a mean leukocyte concentration of 7991.4 × 106/L and 0.1 × 106/L, respectively. Patients were evaluated at baseline and thereafter at 2, 6, and 12 months for the primary outcome, the International Knee Documentation Committee (IKDC) subjective score; and for secondary outcomes, the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, EuroQol–visual analog scale (EQ-VAS), and Tegner score. Results: No differences between groups were observed in terms of absolute values or improvement of the clinical scores across all follow-up intervals. The mean IKDC subjective score at baseline and 12 months improved from 45.6 to 60.7 in the LR-PRP group as compared with 46.8 to 62.9 in the LP-PRP group (P = .626). No severe adverse events were described in either group, although 15 mild adverse events (knee pain or swelling) were reported: 12.2% for LR-PRP and 4.7% for LP-PRP (P = .101). No statistically significant difference was also found between LR-PRP and LP-PRP in terms of failures (7.8% vs 3.5%, P = .331). Conclusion: This double-blind randomized trial showed that 3 intra-articular LR-PRP or LP-PRP injections produced similar clinical improvement in the 12 months of follow-up in patients with symptomatic knee OA. Both treatment groups reported a low number of adverse events, without intergroup differences. The presence of leukocytes did not significantly affect the clinical results of PRP injections. Registration: NCT02923700 (ClinicalTrials.gov identifier).