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  • Intra-articular Injection for the Management of Rheumatoid Arthritis Patients with Knee Osteoarthritis-Current Evidence and Future Prospects

    Mini Review

    Intra-articular injection of hyaluronic acid (HA) is well known to improved pain and function in patients with osteoarthritis (OA) [1,2]. As for rheumatoid arthritis (RA) patients with knee osteoarthritis, current medication for injection therapy includes steroid, hyaluronic acid, and platelet-rich plasma (PRP). In this article, we collected current studies regarding to this issue and suggest future possible research direction.

    Intra-articular corticosteroid injection is long to be known as a useful adjunct therapy for the management of RA. Intra-articular injection of corticosteroid has been shown to provide clinical benefit up to 6 months and even longer [3]. From a pharmacological point of view, corticosteroid injection is able to decrease the expression of citrullinated proteins, monoclonal antibody F95, and peptidylarginine deiminase [4] in RA synovium, and the side effect is low. According to the subanalyses from the BeSt study, [4] eight-year radiographs showed similar damage in injected joints and noninjected joints. From a clinical point of view, corticosteroid injection remains a safe and cost effective way for managing RA-related OA.

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  • Hyaluronic Acid and Platelet-rich Plasma in the Treatment of Knee Osteoarthritis: A Systematic Review

    Abstract

    Introduction: Due to loss of function and intolerable pain associated with Osteoarthritis (OA), this condition is regarded as one of the major causes of disability, worldwide. Aging and obesity are regarded as two fundamental causes of knee OA. The aim of this study was to review the literature on the efficacy of hyaluronic acid in compression [z1]

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  • Clinical Trials with Mesenchymal Stem Cells: An Update

    Abstract

    In the last year, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. Currently the most commonly used adult stem cells in regenerative medicine, MSCs can be isolated from several tissues, exhibit a strong capacity for replication in vitro, and can differentiate into osteoblasts, chondrocytes, and adipocytes. However, heterogeneous procedures for isolating and cultivating MSCs among laboratories have prompted the International Society for Cellular Therapy (ISCT) to issue criteria for identifying unique populations of these cells. Consequently, the isolation of MSCs according to ISCT criteria has produced heterogeneous, non-clonal cultures of stromal cells containing stem cells with different multipotential properties, committed progenitors, and differentiated cells. Though the nature and functions of MSCs remain unclear, non-clonal stromal cultures obtained from bone marrow and other tissues currently serve as sources of putative MSCs for therapeutic purposes, and several findings underscore their effectiveness in treating different diseases. To date, 493 MSC-based clinical trials, either complete or ongoing, appear in the database of the US National Institute of Health. In the present paper, we provide a comprehensive review of MSC-based clinical trials conducted worldwide that scrutinizes MSCs\' biological properties, elucidates recent clinical findings and clinical trial phases of investigation, highlights MSCs\' therapeutic effects, and identifies principal criticisms of the use of these cells. In particular, we analyze clinical trials using MSCs for representative diseases, including hematological disease, graft-versus-host disease, organ transplantation, diabetes, inflammatory diseases, and diseases in the liver, kidney, and lung, as well as cardiovascular, bone and cartilage, neurological, and autoimmune diseases.

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  • Intraosseous infiltration of platelet-rich plasma for severe knee osteoarthritis

    Abstract

    We describe a new technique of platelet-rich plasma (PRP) infiltration for the treatment of severe knee osteoarthritis. PRP intra-articular infiltration is a promising treatment for knee osteoarthritis, but it still has some limitations in high-degree osteoarthritis. Diagnosis of osteoarthritis is based on clinical and radiographic findings, and patients with grade III or IV knee tibiofemoral osteoarthritis based on the Ahlbפck scale are considered candidates for this technique. The technique consists of performing intraosseous infiltration of PRP into the subchondral bone, which acts on this tissue and consequently on cartilage-bone communication. Although the intraosseous injection hinders the conventional knee intra-articular infiltration, it allows an extension of the range of action of the PRP, which acts directly on the subchondral bone, which is involved in the progression of osteoarthritis. Thus this technique involves a new administration of PRP that can delay knee arthroplasty; moreover, it can be applied for not only severe osteoarthritis but also other pathologies in which the subchondral bone is critical in the etiology, such as necrosis and osteochondral lesions.

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  • Peroneus Longus Rupture at Its Origin Managed With Platelet Rich Plasma

    Abstract

    Tears of the peroneus longus muscle are unusual, and typically involve the distal insertion at the musculotendon junction. Although tears of the mid-portion of the peroneus longus muscle/tendon complex have been reported, no reports of a tear at the origin of the peroneus muscle have been published, to the authors\' knowledge. Herein a case of proximal peroneus longus muscle tear and its subsequent management with platelet rich plasma is reported.

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  • Knee cartilage defect: marrow stimulating techniques

    Abstract

    Painful chondral defects of the knee are very difficult problems. The incidence of these lesions in the general population is not known since there is likely a high rate of asymptomatic lesions. The rate of lesions found during arthroscopic exam is highly variable, with reports ranging from 11 to 72

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  • Therapeutic application of mesenchymal stem cells in osteoarthritis

    Abstract

    Introduction: Osteoarthritis (OA) is a degenerative disease characterized by cartilage degradation and subchondral bone alterations. This disease represents a global public health problem whose prevalence is rapidly growing with the increasing aging of the population. With the discovery of mesenchymal stem cells (MSC) as possible therapeutic agents, their potential for repairing cartilage damage in OA is under investigation.

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  • Clinical Outcome of Bone Marrow Concentrate in Knee Osteoarthritis

    Abstract

    Background: Knee osteoarthritis is an increasing health concern in the adult population. Nonsurgical treatment options for pain reduction and function improvement are limited in number and provide only short-term relief. The potential of regenerative therapies to go beyond temporary symptom reduction and delay or negate the need for total knee joint arthroplasty is enticing to both patients and providers.

    Purpose: This study evaluated the clinical efficacy of autologous intra-articular bone marrow concentrate with autologous lipoaspirate as a treatment option for osteoarthritis of the knee. Additionally, bone marrow concentrate samples from a patient population subset not necessarily enrolled in this study, but IRB approved, were sent for outside laboratory analysis.

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  • Cartilage Regeneration: How Do We Meet the Increasing Demands of an Ageing Population?

    Editorial

    Globally, hundreds of millions of people are affected by musculoskeletal disorders (~10 million in the UK) [1]. Data presented from a pan-European study showed that one in three people are affected by musculoskeletal pain and disorders of the musculoskeletal system are the most common work-related health problem. From a survey of individuals who retired early on medical grounds or were on long-term sickness benefit, up to 60% cited musculoskeletal pain as the cause [2]. As well as these societal implications there is a significant economic cost associated with musculoskeletal health. The National Health Service (NHS) spends over

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  • Efficacy and safety profile of a compound composed of platelet-rich plasma and hyaluronic acid in the treatment for knee osteoarthritis (preliminary results)

    Abstract

    Background

    The combined use of hyaluronic acid and platelet-rich plasma has never been reported in the treatment for osteoarthritis. Aim of this paper was to evaluate the efficacy of this association and to compare retrospectively these results with those of a cohort of patients treated with platelet-rich plasma only.

    Materials and methods

    Subjects with mild-to-moderate knee osteoarthritis were enrolled. After clinical and ultrasound evaluation, patients received a weekly intra-articular injection of 2

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  • Short-term outcomes of platelet-rich plasma injection for treatment of osteoarthritis of the knee

    Abstract

    Purpose

    To compare the clinical outcomes of osteoarthritis indices (WOMAC and Lequesne scores) and adverse events in the treatment of osteoarthritis (OA) of the knee with platelet-rich plasma (PRP) versus hyaluronic acid (HA) or placebo.

    Methods

    A systematic review and meta-regression were performed to compare outcomes between PRP injections versus HA or placebo. Relevant randomized control trials were identified from Medline and Scopus from date of inception to 13 August 2015.

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  • RANTES and SDF-1 Are Keys in Cell-based Therapy of TMJ Osteoarthritis

    Abstract

    The present study aimed to investigate the therapeutic effect of injections of local bone marrow mesenchymal stem cells (BMSCs) on osteoarthritis (OA) of the temporomandibular joint (TMJ) and to explore the role of stromal cell-derived factor 1 (SDF-1) and regulated on activation, normal T-cell expressed and secreted (RANTES) in this effect. Fundamentally, OA of the TMJ was induced by unilateral anterior crossbite in mice. Exogenous green fluorescent protein-labeled BMSCs (GFP-BMSCs) were weekly injected into the TMJ region for 4, 8, and 12 wk. The reparative effects of exogenous GFP-BMSCs were investigated by morphological observation and micro-computed tomography. The differentiation of GFP-BMSCs in the cartilage was examined by double immunofluorescence of GFPs with type II collagen, and the expression of related factors in the condylar cartilage was quantified by real-time polymerase chain reaction. The role of RANTES and SDF-1 in the therapeutic effect of exogenous BMSCs was examined by both in vitro and in vivo studies. The OA cartilage of the TMJ displays a synchronous increase in SDF-1 and RANTES expression and a higher capability of attracting the migration of GFP-BMSCs. The implanted GFP-BMSCs differentiated into type II collagen-positive cells and reversed cartilage degradation and subchondral bone loss in mice with OA of the TMJ. The migration of GFP-BMSCs towards OA cartilage and the rescuing effect of GFP-BMSC injections were impaired by the inhibitors of C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 1 (CCR1), which are the receptors of SDF-1 and RANTES, respectively. Our data indicated that SDF-1/CXCR4 and RANTES/CCR1 signals are pivotal and function synergistically in the recruitment of GFP-BMSCs towards degraded cartilage in mice OA of the TMJ.

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  • A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis

    Abstract

    Background

    Prior studies describing the treatment of symptomatic knee osteoarthritis with injections of bone marrow concentrate have provided encouraging results. The relationship between the cellular dose contained within the bone marrow concentrate and efficacy of the treatment, however, is unclear. In the present study we describe clinical outcomes for symptomatic knee osteoarthritis in relation to higher and lower cell concentrations contained within a bone marrow concentrate treatment protocol.

    Methods

    Data from an ongoing patient registry was culled to identify 373 patients that received bone marrow concentrate injections for the treatment of 424 osteoarthritic knee joints. The clinical scales for these patients were assessed at baseline and then tracked post-procedure at 1, 3, 6 and 12

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  • Mesenchymal Stem Cells in Regenerative Medicine: Focus on Articular Cartilage and Intervertebral Disc Regeneration

    Abstract

    Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton\'s jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.

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  • Sonographically guided obturator internus injections: techniques and validation

    Abstract

    OBJECTIVES: The primary purpose of this investigation was to describe and validate sonographically guided techniques for injecting the obturator internus (OI) muscle or bursa using a cadaveric model.

    METHODS: A single experienced operator completed 10 sonographically guided OI injections in 5 unembalmed cadaveric pelvis specimens (4 female and 1 male, ages 71-89 years with body mass indices of 15.5-24.2 kg/m2). Four different techniques were used: (1) OI tendon sheath (4 injections), (2) OI intramuscular (2 injections), (3) OI bursa trans-tendinous (2 injections), and (4) OI bursa short-axis (2 injections). In each case, the operator injected 1.5 mL of diluted yellow latex using direct sonographic guidance and a 22-gauge, 87.5-mm (3

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  • Effectiveness of a single platelet-rich plasma injection to promote recovery in rugby players with ankle syndesmosis injury

    Abstract

    Aims To determine whether a single ultrasound-guided platelet-rich plasma (PRP) injection into the anterior inferior tibiofibular ligament (AITFL) reduces the time for rugby athletes to return to function and match play following MRI confirmed ankle syndesmosis injury.

    Methods Cohort controlled pilot study. 10 Rugby Union players were recruited during the 2014 season, and consented to receive a single autologous PRP injection into the AITFL within 14 €…days of MRI confirmed ankle syndesmosis injury. A historical control group included 11 comparable Rugby Union players between 2011 and 2013 who were treated conservatively with the same inclusion criteria and rehabilitation protocol as the intervention group. Participants followed a standardised rehabilitation protocol involving simple milestones for progression. Early functional tests were performed 2 €…weeks after the removal of the CAM (controlled ankle motion) boot. Time to return to play was recorded. Repeat functional testing occurred within 1 €…week of return to play.

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  • Intraarticular Injection of Allogenic Mesenchymal Stem Cells has a Protective Role for the Osteoarthritis

    Background:

    Researchers initially proposed the substitution of apoptotic chondrocytes in the superficial cartilage by injecting mesenchymal stem cells (MSCs) intraarticularly. This effect was termed as bio-resurfacing. Little evidence supporting the treatment of osteoarthritis (OA) by the delivery of a MSC suspension exists. The aim of this study was to investigate the effects of injecting allogenic MSCs intraarticularly in a rat OA model and to evaluate the influence of immobility on the effects of this treatment.

    Methods: We established a rat knee OA model after 4 and 6 weeks and cultured primary bone marrow MSCs. A MSC suspension was injected into the articular space once per week for 3 weeks. A subgroup of knee joints was immobilized for 3 days after each injection, while the remaining joints were nonimmobilized. We used toluidine blue staining, Mankin scores, and TdT-mediated dUTP-biotin nick end labeling staining to evaluate the therapeutic effect of the injections. Comparisons between the therapy side and the control side of the knee joint were made using paired t-test, and comparisons between the immobilized and nonimmobilized subgroups were made using the unpaired t-test. A P value < 0.05 was considered significant.

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  • Intramuscular oxygen-ozone therapy in the treatment of acute back pain with lumbar disc herniation: a multicenter, randomized, double-blind, clinical trial of active and simulated lumbar paravertebral injection

    Abstract

    STUDY DESIGN: Multicenter randomized, double-blind, simulated therapy-controlled trial in a cohort of patients with acute low back pain (LBP) due to lumbar disc herniation (LDH).

    OBJECTIVE: To assess the benefit of intramuscular-paravertebral injections of an oxygen-ozone (O2O3) mixture.

    SUMMARY OF BACKGROUND DATA: Recent findings have shown that O2O3 therapy can be used to treat LDH that fails to respond to conservative management. However, these findings are based on intradiscal/intraforaminal O2O3 injection, whereas intramuscular-paravertebral injection is the technique used most in clinical practice in Italy and other Western countries.

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  • Platelet-rich plasma for chronic lateral epicondylitis: Is one injection sufficient?

    Abstract

    Introduction

    Chronic lateral epicondylitis is generally treated using nonsurgical methods including physiotherapy and infiltrations of cortisone or platelet-rich plasma (PRP). The latter is known for its simple application as well as associated low risk of adverse events, which lend to its widespread use in treating various musculoskeletal conditions. There is limited evidence on the effectiveness of PRP injections to optimally treat chronic lateral epicondylitis. This study explored the effectiveness of single or repeated injections for patients with symptoms that spanned 6 months or more and were unresponsive to alternate conservative measures.

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  • Platelet-Rich Plasma Injection for Symptomatic Knee Osteoarthritis

    Abstract

    Background: Platelet-rich plasma (PRP) is plasma of enriched platelets with high concentration of platelet granules and growth factors. The platelet growth factors have a great potential of wound and connective tissue healing used to treat cartilage lesions and retarding the progression of knee osteoarthritis

    .

    Objectives: This study was designed to evaluate PRP injection results in knee osteoarthritis.

    Patients and Methods: This was a case-series study of 39 patients and all of them had three injections of PRP for the involved knee (every two weeks) and they were followed up at two weeks, two months and six months post-injection of PRP. All included patients filled the WOMAC (western Ontario and Mcmaster universities arthritis index) standardized and translated to our national language and culture. We analyzed the collected scores of before initiation of PRP injections, the second week, the second month and the sixth month after injections into the knees.

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