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  • Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options

    Abstract

    Purpose: This study was performed to compare the efficacy of treatment in three groups of patients with knee osteoarthritis (OA) given an intra-articular injection of platelet-rich plasma (PRP), hyaluronic acid (HA) or ozone gas.

    Methods: A total of 102 patients with mild-moderate and moderate knee OA who presented at the polyclinic with at least a 1-year history of knee pain and VAS score ≥4 were randomly separated into three groups. Group 1 (PRP group) received intra-articular injection of PRP ×— 2 doses, Group 2 (HA group) received a single dose of HA, and Group 3 (Ozone group) received ozone ×— four doses. Weight-bearing anteroposterior-lateral and Merchant\'s radiographs of both knees were evaluated. WOMAC and VAS scores were applied to all patients on first presentation and at 1, 3, 6 and 12 months.

    Results: At the end of the 1st month after injection, significant improvements were seen in all groups. In the 3rd month, the improvements in WOMAC and VAS scores were similar in Groups 1 and 2, while those in Group 3 were lower (p < 0.001). At the 6th month, while the clinical efficacies of PRP and HA were similar and continued, the clinical effect of ozone had disappeared (p < 0.001). At the end of the 12th month, PRP was determined to be both statistically and clinically superior to HA (p < 0.001).

    Conclusion: In the treatment of mild-moderate knee OA, PRP was more successful than HA and ozone injections, as the application alone was sufficient to provide at least 12 months of pain-free daily living activities.

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  • The Chondrogenic Effect of Intra-articular Hypertonic-dextrose (prolotherapy) in Severe Knee Osteoarthritis

    Abstract

    Background: Dextrose injection is reported to improve KOA-related clinical outcomes, but its effect on articular cartilage is unknown. A chondrogenic effect of dextrose injection has been proposed.

    Objective: To assess biological and clinical effects of intra-articular hypertonic dextrose injections (prolotherapy) in painful knee osteoarthritis (KOA).

    Design: Case series with blinded arthroscopic evaluation before and after treatment.

    Setting: Physical medicine and day surgery practice.

    Participants: Symptomatic KOA for at least 6 months, arthroscopy-confirmed medial compartment exposed subchondral bone, and temporary pain relief with intra-articular lidocaine injection.

    Intervention: Four to six monthly 10 mL intra-articular injections with 12.5% dextrose.

    Main outcome measures: Visual cartilage growth assessment of 9 standardized medial condyle zones in each of 6 participants by three arthroscopy readers masked to pre/post injection status (total 54 zones evaluated per reader); biopsy of a cartilage growth-area post-treatment, evaluated using H&E and Safranin-O stains, quantitative polarized light microscopy, and immunohistologic cartilage typing; self-reported knee specific quality of life using the Western Ontario McMaster University Osteoarthritis Index (WOMAC, 0-100 points).

    Results: Six participants (1 female) with median age of 71, WOMAC composite score of 57.5 points and a 9-year pain duration received a median 6 dextrose injections and follow-up arthroscopy at 7.75 (4.5-9.5) months. In 19 of 54 zone comparisons all three readers agreed that the post-treatment zone showed cartilage growth compared with the pre-treatment zone. Biopsy specimens showed metabolically active cartilage with variable cellular organization, fiber parallelism, and cartilage typing patterns consistent with fibro- and hyaline-like cartilage. Compared with baseline status, the median WOMAC score improved 13 points (p=.013). Self-limited soreness after methylene-blue instillation was noted.

    Conclusions: Positive clinical and chondrogenic effects were seen after prolotherapy with hypertonic dextrose injection in symptomatic grade IV KOA participants suggesting disease-modifying effects and the need for confirmation in controlled studies. Minimally invasive arthroscopy (single-compartment, single-portal) enabled collection of robust intra-articular data.

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  • Five and ten year follow-up on intradiscal ozone injection for disc herniation

    Abstract

    Background: Disc herniation is the most common cause for spinal surgery and many clinicians employ epidural steroid injections with limited success. Intradiscal injection of ozone gas has been used as an alternative to epidural steroids and surgical discectomy. Early results are positive but long-term data are limited.

    Methods: One hundred and eight patients with confirmed contiguous disc herniation were treated with intradiscal injection of ozone in 2002-2003. One-hundred seven patients were available for telephone follow-up at 5 years. Sixty patients were available for a similar telephone follow-up at ten years. Patients were asked to describe their clinical outcome since the injection. Surgical events were documented. MRI images were reviewed to assess the reduction in disc herniation at six months.

    Results: MRI films demonstrated a consistent reduction in the size of the disc herniation. Seventy-nine percent of patients had a reduction in herniation volume and the average reduction was 56%. There were 19 patients that ultimately had surgery and 12 of them occurred in the first six months after injection. One of these 12 was due to surgery at another level. Two surgeries involved an interspinous spacer indicated by stenosis or DDD. All other surgeries were discectomies. Of the patients that avoided surgery 82% were improved at 5 years and 88% were improved at 10 years. Other than subsequent surgeries, no spine-related complications were experienced.

    Conclusions/Level of Evidence: We conclude that ozone is safe and effective in approximately 75% of patients with disc herniation and the benefit is maintained through ten years. This is a retrospective review and randomized trials are needed.

    Clinical Relevance: Intradiscal ozone injection may enable patients to address their pain without multiple epidural injections and surgery. The benefit of ozone is durable and does not preclude future surgical options. The risk reward profile for this treatment is favorable.

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  • Intra-articular Treatment of Knee Osteoarthritis: from Anti-inflammatories to Products of Regenerative Medicine

    Abstract

    Objectives: Knee osteoarthritis (OA)1 is a debilitating condition that may ultimately require total knee arthroplasty (TKA).2 Non-operative treatments are bracing, oral analgesics, physical therapy, and intra-articular knee injection (IAKI).3 The objective of this paper is to provide a systematic literature review regarding intra-articular treatment of knee OA and insight into promising new products of regenerative medicine that may eventually have a substantial effect on treatment.

    Methods: A literature search was executed using Medline, Cochrane, and Embase with keywords \"knee osteoarthritis\" and \"injection.\" Specifically, 45 articles that discussed intra-articular knee injection using corticosteroids, hyaluronic acid, analgesics, local anesthetics, and newer products of regenerative medicine, such as platelet-rich plasma (PRP)4 and mesenchymal stem cells (MSC),5 were analyzed. Of these, eleven were level 1, three were level 2, twelve were level 3, two were level 4, and seventeen were level 5 evidence. Papers included animal models.

    Results: Local anesthetics have potential side effects and may only be effective for a few hours. Morphine and ketorolac may provide significant pain relief for 24 hours. Corticosteroids may give patients weeks to months of effective analgesia, but complications may occur, such as systemic hyperglycemia, septic arthritis, and joint degradation . Hyaluronic acid is a natural component of synovial fluid, but efficacy with respect to analgesia is controversial. Platelet-rich plasma formulations, autologous conditioned serum, autologous protein solution, and mesenchymal stem cell injections contain anti-inflammatory molecules and have been proposed to attenuate joint destruction or potentially remodel the joint.

    Conclusions: Currently, knee OA treatment does not address the progressively inflammatory environment of the joint. More investigation is needed regarding products of regenerative medicine, but they may ultimately have profound implications in the way knee OA is managed.

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  • Regeneration of articular cartilage using adipose stem cells

    Abstract

    Articular cartilage (AC) has limited potential for self-regeneration and damage to AC eventually leads to the development and progression of osteoarthritis (OA). Cell implantation strategies have emerged as a new treatment modality to regenerate AC. Adipose stem cells/adipose-derived stromal cells (ASCs) have gained attention due to their abundance, excellent proliferative potential, and minimal morbidity during harvest. These advantages lower the cost of cell therapy by circumventing time-consuming procedure of culture expansion. ASCs have drawn attention as a potential source for cartilage regeneration since the feasibility of chondrogenesis from ASCs was first reported. After several groups reported inferior chondrogenesis from ASCs, numerous methods were devised to overcome the intrinsic properties. Most in vivo animal studies have reported good results using predifferentiated or undifferentiated, autologous or allogeneic ASCs to regenerate cartilage in osteochondral defects or surgically-induced OA. In this review, we summarize literature on the isolation and in vitro differentiation processes of ASCs, in vivo studies to regenerate AC in osteochondral defects and OA using ASCs, and clinical applications of ASCs.

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  • Clinical Outcomes of Biologic Treatment for Chronic Tendinopathy

    Abstract

    Biological interventions, such as ultrasound guided platelet rich plasma (PRP) injections, are a second line treatment worth considering for recalcitrant tendinopathy, but efficacy and effectiveness have not been established yet. The use of PRP has been most commonly studied in lateral epicondylitis, with nine randomized controlled trials and seven prospective controlled studies in the medical literature. Corticosteroid injection was used as the comparator in six studies, autologous blood in three, and local anesthetic agents in two studies. Recent meta-analyses showed that PRP and autologous blood are superior to corticosteroids in pain reduction and ameliorating functionality in epicondylitis. PRP efficacy on supraspinatus tears are controversial, and PRP is better than controls in two out of five studies, when compared with corticosteroids and dry needling. Patellar tendinopathy is examined in four controlled studies, and eight case series, PRP ameliorated outcomes but not in all cases. Whether more than one injection should be given is under discussion. Achilles tendinopathy was examined in three prospective controlled studies (a single injection), and six case series. Patients showed improvements regarding baseline values, but two controlled studies failed to reveal differences with controls. Pooling data across studies is challenging because of heterogeneity in outcome scores and comparators. Tendinopathy progression and outcomes are poorly monitored with self-reported questionnaires that are not sensitive enough to discriminate local changes. Molecular indicators of tendon health and disease can help to assess whether the condition progress or heal after biological interventions. The international consensus about the design of clinical studies should be pursued.

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  • Platelet-rich plasma limits the nerve injury caused by 10% dextrose in the rabbit median nerve

    Abstract

    Introduction: We evaluated the effect of platelet-rich plasma (PRP) injection in a rabbit model of dextrose-induced median nerve injury.

    Methods: New Zealand white rabbits (n = 15) were divided randomly into 3 groups. Three different regimens (group 1: 0.1 ml saline; group 2: 10% dextrose with PRP; group 3: 10% dextrose with saline) were injected within the carpal tunnel. Electrophysiological and histological findings were evaluated 12 weeks after the injection.

    Results: The mean median motor latency in group 3 was significantly longer than that in groups 1 and 2. The cross-sectional area of the median nerve and subsynovial connective tissue thickness in group 3 were significantly larger than those in groups 1 and 2.

    Conclusion: PRP injection may be effective in controlling median nerve injury, as demonstrated by improvement in electrophysiological and histological findings 12 weeks after dextrose injection.

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  • A new strategy to tackle severe knee osteoarthritis: Combination of intra-articular and intraosseous injections of Platelet Rich Plasma

    Abstract

    Introduction: Knee osteoarthritis (KOA) is a mechanically induced, cytokine and enzyme-mediated disorder involving all the joint tissue of the knee. Rebuilding a physiological-homeostatic network at the tissue level following knee organ failure, such as in severe KOA, is a daunting task with therapeutic targets encompassing the articular cartilage, synovium and subchondral bone. Intraarticular infiltration of plasma rich in growth factors (PRP) has emerged as a promising symptomatic approach, although it is insufficient to reach the subchondral bone.

    Areas covered: This review addresses current molecular and cellular data in joint homeostasis and osteoarthritis pathophysiology. In particular, it focuses on changes that subchondral bone undergoes in knee osteoarthritis and evaluates recent observations on the crosstalk among articular cartilage, subchondral bone and synovial membrane. In addition, we review some mechanistic aspects that have been proposed and provide the rationale for using PRP intraosseously in KOA.

    Expert opinion: The knee joint is a paradigm of autonomy and connectedness of its anatomical structures and tissues from which it is made. We propose an innovative approach to the treatment of severe knee osteoarthritis consisting of a combination of intraarticular and intraosseous infiltrations of PRP, which might offer a new therapeutic tool in KOA therapy.

    Disclaimer: As a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also.

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  • Hyaluronic acid induces the release of growth factors from platelet-rich plasma

    Abstract

    Background/Objective: Platelet-rich plasma (PRP) and hyaluronic acid (HA) injection are both therapeutic options for osteoarthritis and chronic tendinopathy. Although several comparative studies on the two have been published, the effects of mixing PRP and HA are not fully understood. The purpose of this study is to investigate the influence of HA on platelets in PRP by measuring releasing growth factors.

    Methods: PRP was produced from nine healthy adult volunteers (mean age, 32.8 ± 2.9 years; range, 29-37) with a commercial separation system. HA of weight-average molecular weight of 50-120 kDa was used. PRP group (PRP 1 mL + phosphate buffered saline 0.2 mL) and PRP + HA group (PRP 1 mL + HA 0.2 mL) were incubated at 37 °C for 2 hours. The amounts of transforming growth factor β1 (TGF-β1) and platelet-derived growth factor (PDGF-AA) released from the PRP and PRP + HA samples were measured on Day 0, Day 3, and Day 5. In addition, the same growth factors on Day 5 were measured for PRP + high HA group (PRP 1 mL + HA 0.6 mL) with five donors. After collecting all of the samples on Day 5, the remaining gels were observed with Giemsa stain. Statistical analyses were performed using paired t tests to compare the PRP and HA groups at each time point, and a one-way analysis of variance (one-way ANOVA) with Tukey post hoc tests was used to compare the PRP, PRP + HA, and PRP + high HA groups.

    Conclusion: The levels of growth factors released by PRP on Day 5 were increased by the addition of HA. A mixture of PRP and HA may be a more effective therapy than PRP or HA alone for osteoarthritis and tendinopathy.

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  • Prolotherapy for Knee Osteoarthritis: A Descriptive Review

    Abstract

    Knee osteoarthritis (KOA) is a common chronic disease of high patient and societal impact. The etiology is multifactorial; pain sources include both intra- and extra-articular tissues. A number of alternative therapies have been assessed for KOA. Patients are often refractory to best-practice conservative management, and the development of new therapy has been called for by national health services groups. Prolotherapy is an outpatient therapy for chronic musculoskeletal pain including KOA. Protocols include injection at attachments of soft-tissue supportive structures such as ligaments and tendons, and within intra-articular spaces. Although the understanding of mechanism is not well understood, a small but growing body of literature suggests that prolotherapy may be appropriate therapy for carefully selected patients refractory to conventional treatment. This article summarizes evidence from basic and clinical science for use of prolotherapy among patients with KOA.

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  • Chronic Plantar Fasciitis: Effect of Platelet-Rich Plasma, Corticosteroid, and Placebo

    Abstract

    Plantar fasciitis is a common cause of heel pain. It is a disabling disease in its chronic form. It is a degenerative tissue condition of the plantar fascia rather than an inflammation. Various treatment options are available, including nonsteroidal anti-inflammatory drugs, corticosteroid injections, orthosis, and physiotherapy. This study compared the effects of local platelet-rich plasma, corticosteroid, and placebo injections in the treatment of chronic plantar fasciitis. In this double-blind study, patients were divided randomly into 3 groups. Local injections of platelet-rich plasma, corticosteroid, or normal saline were given. Patients were assessed with the visual analog scale for pain and with the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle and Hindfoot score before injection, at 3 weeks, and at 3-month follow-up. Mean visual analog scale score in the platelet-rich plasma and corticosteroid groups decreased from 7.44 and 7.72 preinjection to 2.52 and 3.64 at final follow-up, respectively. Mean AOFAS score in the platelet-rich plasma and corticosteroid groups improved from 51.56 and 55.72 preinjection to 88.24 and 81.32 at final follow-up, respectively. There was a significant improvement in visual analog scale score and AOFAS score in the platelet-rich plasma and corticosteroid groups at 3 weeks and at 3-month follow-up. There was no significant improvement in visual analog scale score or AOFAS score in the placebo group at any stage of the study. The authors concluded that local injection of platelet-rich plasma or corticosteroid is an effective treatment option for chronic plantar fasciitis. Platelet-rich plasma injection is as effective as or more effective than corticosteroid injection in treating chronic plantar fasciitis. [Orthopedics.]

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  • Allogeneic Mesenchymal Stem Cells in Combination with Hyaluronic Acid for the Treatment of Osteoarthritis in Rabbits

    Abstract

    Mesenchymal stem cell (MSC)-based therapies may aid in the repair of articular cartilage defects. The purpose of this study was to investigate the effects of intraarticular injection of allogeneic MSCs in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis in rabbits. Allogeneic bone marrow-derived MSCs were isolated and cultured under hypoxia (1% O2). After 8 weeks following ACLT, MSCs suspended in hyaluronic acid (HA) were injected into the knees, and the contralateral knees were injected with HA alone. Additional controls consisted of a sham operation group as well as an untreated osteoarthritis group. The tissues were analyzed by macroscopic examination as well as histologic and immunohistochemical methods at 6 and 12 weeks post-transplantation. At 6 and 12 weeks, the joint surface showed less cartilage loss and surface abrasion after MSC injection as compared to the tissues receiving HA injection alone. Significantly better histological scores and cartilage content were observed with the MSC transplantation. Furthermore, engraftment of allogenic MSCs were evident in surface cartilage. Thus, injection of the allogeneic MSCs reduced the progression of osteoarthritis in vivo.

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  • Plantar fasciitis: Outcome evaluation of plantar fasciitis treated with PRP against steroid injection

    Abstract

    Plantar fasciitis is the most com mmon cause of heel pain which seems difficult t to treat in its most chronic and severe forms. Earlier treatments, including orthoses, non steroidacial anti-inflammatory drugs, and steroid injections aree paucity of supportive clinical evidence but ca arry the potential for serious complication and perm manent disability. Platelet-rich plasma (PRP) has recently been demonstrated to be helpful in m managing chronic severe plantar fasciitis when ot ther techniques have failed. The purpose of this study y was to assess the safety and preliminary clinicaal results of platelet-rich plasma injections for treat ting chronic plantar fasciitis. 163 consecutive p patients with chronic plantar fasciitis receiving injectiions of PRP and 158 patients for steroid injecti ions into the plantar fascia were assessed 12 monthss after the procedure. The visual analogue scalee (VAS) for pain was used to evaluate the clinical re esults. According to criteria VAS score, at 12 m months of follow-up, results were rated as excellen nt in all PRP injected patients, good and poor r in steroid injected patients. In PRP injection, VAS (m mean) for pain was significantly decreased from 88.6 before treatment to 0.3 at the last follow-up. PRP P injection has safety and efficiency as treatmen nt for plantar fasciitis with no side effects and complications.

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  • Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin In Vitro and In Vivo

    Abstract

    Objective: Lubricin expression in the superficial cartilage will be a crucial factor in the success of carti-lage regeneration. Mesenchymal stem cells (MSCs) are an attractive cell source and theuse of aggregates of MSCs has some advantages in terms of chondrogenic potential andefficiency of cell adhesion. Lubricin expression in transplanted MSCs has not been fully elu-cidated so far. Our goals were to determine (1) whether cartilage pellets of human MSCs expressed lubricinin vitro chondrogenesis, (2) whether aggregates of human MSCs pro-moted lubricin expression, and (3) whether aggregates of MSCs expressed lubricin in the superficial cartilage after transplantation into osteochondral defects in rats.

    Methods: For in vitro analysis, human bone marrow (BM) MSCs were differentiated into cartilage by pellet culture, and also aggregated using the hanging drop technique. For an animal study, aggregates of BM MSCs derived from GFP transgenic rats were transplanted to the osteo- chondral defect in the trochlear groove of wild type rat knee joints. Lubricin expression was mainly evaluated in differentiated and regenerated cartilages.

    Results: In in vitro analysis, lubricin was detected in the superficial zone of the pellets and condi-tioned medium. mRNA expression of Proteoglycan4 (Prg4), which encodes lubricin, in pel-lets was significantly higher than that of undifferentiated MSCs. Aggregates showed different morphological features between the superficial and deep zone, and the Prg4 mRNA expression increased after aggregate formation. Lubricin was also found in the aggregate. In a rat study, articular cartilage regeneration was significantly better in the MSC group than in the control group as shown by macroscopical and histological analysis.

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  • Long-term effect of Prolotherapy on symptomatic rotator cuff tendinopathy

    Abstract

    Introduction: The objective of this study was to assess a long-term clinical effect of Prolotherapy on chronic symptomatic rotator cuff tendinopathy.

    Methods: We conducted a retrospective, uncontrolled study in the outpatient setting with 12 months follow-up. Adults diagnosed clinically and radiologically with rotator cuff tendinopathy that has been persisting for a minimum of six months were included. Patients received 15% extra-articular and 25% intra-articular hyperosmolar dextrose injections, repeated at weeks 5, 9, 13, 17 and 21. Primary outcome measure was validated Shoulder Pain and Disability Index (SPADI). Secondary outcome measure was validated visual pain analogue scale (VAS 0-10). The third outcome measures were patient\'s satisfaction with Prolotherapy and adverse reactions after injections.

    Results: Twenty-one patients, 14 male and 7 female were treated with 6 sessions of hyperosmolar dextrose Prolotherapy repeated every 4 weeks. Average SPADI before starting the treatment was 73.995

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  • Adipose stem cells differentiated chondrocytes regenerate damaged cartilage in rat model of Osteoarthritis

    Abstract

    Transplantation of mesenchymal stem cells (MSCs) or autologous chondrocytes has been shown to repair damages to articular cartilage due to osteoarthritis (OA). However survival of transplanted cells is considerably reduced in the osteoarthritic environment and it affects successful outcome of the transplantation of the cells. Differentiated chrondroytes derived from adipose stem cells have been proposed as an alternative source and our study investigated this possibility in rats. We investigated the regenerative potential of ASCs and DCs in osteoarthritic environment in the repair of cartilage in rats. We found that ASCs maintained fibroblast morphology in vitro and also expressed CD90 and CD29. Furthermore, ASCs differentiated into chondrocytes, accompanied by increased level of proteoglycans and expression of chondrocytes specific genes, such as, Acan and Col2a1. Histological examination of transplanted knee joints showed regeneration of cartilage tissue compared to control OA knee joints. Increase in gene expression for Acan, Col2a1 with concomitant decrease in the expression of Col1a1 suggested formation of hyaline like cartilage. A significant increase in differentiation index was observed in DCs and ASCs transplanted knee joints (P = 0.0110 vs P = 0.0429) when compared to that in OA control knee joints. Furthermore, transplanted DCs showed increased proliferation along with reduction in apoptosis as compared to untreated control.

    In conclusion, DCs showed better survival and regeneration potential as compared with ASCs in rat model of OA and thus may serve a better option for regeneration of osteoarthritic cartilage.

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  • Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes.

    Abstract

    BACKGROUND: Platelet-rich plasma (PRP) has recently been postulated as a treatment for osteoarthritis (OA). Although anabolic effects of PRP on chondrocytes are well documented, no reports are known addressing effects on cartilage degeneration. Since OA is characterized by a catabolic and inflammatory joint environment, the authors investigated whether PRP was able to counteract the effects of such an environment on human osteoarthritic chondrocytes.

    HYPOTHESIS: Platelet-rich plasma inhibits inflammatory effects of interleukin-1 (IL-1) beta on human osteoarthritic chondrocytes.

    STUDY DESIGN:Controlled laboratory study.

    METHODS: Human osteoarthritic chondrocytes were cultured in the presence of IL-1 beta to mimic an osteoarthritic environment. Medium was supplemented with 0%, 1%, or 10% PRP releasate (PRPr, the active releasate of PRP). After 48 hours, gene expression of collagen type II alpha 1 (COL2A1), aggrecan (ACAN), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, ADAMTS5, matrix metalloproteinase (MMP)13, and prostaglandin-endoperoxide synthase (PTGS)2 was analyzed. Additionally, glycosaminoglycan (GAG) content, nitric oxide (NO) production, and nuclear factor kappa B (NFκB) activation were studied.

    RESULTS: Platelet-rich plasma releasate diminished IL-1 beta-induced inhibition of COL2A1 and ACAN gene expression. The PRPr also reduced IL-1 beta-induced increase of ADAMTS4 and PTGS2 gene expression. ADAMTS5 gene expression and GAG content were not influenced by IL-1 beta or additional PRPr. Matrix metalloproteinase 13 gene expression and NO production were upregulated by IL-1 beta but not affected by added PRPr. Finally, PRPr reduced IL-1 beta-induced NFκB activation to control levels containing no IL-1 beta.

    CONCLUSION: Platelet-rich plasma releasate diminished multiple inflammatory IL-1 beta-mediated effects on human osteoarthritic chondrocytes, including inhibition of NFκB activation.

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  • Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

    Abstract

    Platelet-rich blood derivatives have been widely used in different fields of medicine and stem cell-based tissue engineering. They represent natural cocktails of autologous growth factors, which could provide an alternative for recombinant protein-based approaches. Platelet-rich blood derivatives, such as platelet-rich plasma, have consistently shown to potentiate stem cell proliferation, migration, and differentiation. Here, we review the spectrum of platelet-rich blood derivatives, discuss their current applications in tissue engineering and regenerative medicine, reflect on their effect on stem cells, and highlight current translational challenges.

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  • Does platelet-rich plasma have a role in the treatment of osteoarthritis?

    Abstract

    Platelet-rich plasma (PRP) has been generating considerable attention as an intra-articular treatment to alleviate the symptoms of osteoarthritis. Activated platelets release a host of soluble mediators such as growth factors and cytokines, thereby inducing complex interactions that vary across tissues within the joint. In vivo, PRP may promote chondrocyte proliferation and differentiation. The available data are somewhat conflicting regarding potential effects on synovial cells and angiogenesis modulation. PRP probably exerts an early anti-inflammatory effect, which may be chiefly mediated by inhibition of the NF-κB pathway, a hypothesis that requires confirmation by proof-of-concept studies. It is far too early to draw conclusions about the efficacy of PRP as a treatment for hip osteoarthritis. The only randomized trial versus hyaluronic acid showed no significant difference in effects, and no placebo-controlled trials are available. Most of the randomized trials in knee osteoarthritis support a slightly greater effect in alleviating the symptoms compared to visco-supplementation, most notably at the early stages of the disease, although only medium-term data are available. Many uncertainties remain, however, regarding the best administration regimen. Serious adverse effects, including infections and allergies, seem rare, although post-injection pain is more common than with other intra-articular treatments for osteoarthritis.

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  • Cytokine-release kinetics of platelet-rich plasma according to various activation protocols

    Abstract

    Objectives: This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols.

    Methods: Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay.

    Results: The concentration of cytokine released from PRP varied over time and was influenced by various activation protocols. Ca-only activation had a significant effect on the DS PRPs (where the VEGF, FGF, and IL-1 concentrations were sustained) while Ca/thrombin activation had effects on both SS and DS PRPs (where the PDGF and VEGF concentrations were sustained and the TGF and FGF concentrations were short). The IL-1 content showed a significant increase with Ca-only or Ca/thrombin activation while these activations did not increase the MMP-9 concentration.

    Conclusion: The SS and DS methods differed in their effect on cytokine release, and this effect varied among the cytokines analysed. In addition, low dose of thrombin/calcium activation increased the overall cytokine release of the PRP preparations over seven days, relative to that with a calcium-only supplement or non-activation.

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