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  • Stem Cell Therapies in Orthopaedic Trauma

    Marcucio, Ralph S. PhD; Nauth, Aaron MD; Giannoudis, Peter V. MD, FRCS; Bahney, Chelsea PhD; Piuzzi, Nicolas S. MD; Muschler, George MD; Miclau, Theodore III MD\nJournal of Orthopaedic Trauma December 2015 Vol. 29 - Issue : p S24-S27

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  • Using mesenchymal stem cells as a therapy for bone regeneration and repairing

    Abstract

    Bone is a unique tissue which could regenerate completely after injury rather than heal itself with a scar. Compared with other tissues the difference is that, during bone repairing and regeneration, after the inflammatory phase the mesenchymal stem cells (MSCs) are recruited to the injury site and differentiate into either chondroblasts or osteoblasts precursors, leading to bone repairing and regeneration. Besides these two precursors, the MSCs can also differentiate into adipocyte precursors, skeletal muscle precursors and some other mesodermal cells. With this multilineage potentiality, the MSCs are probably used to cure bone injury and other woundings in the near future. Here we will introduce the recent developments in understanding the mechanism of MSCs action in bone regeneration and repairing.

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  • Endoscopic plantar fasciotomy versus injection of platelet-rich plasma for resistant plantar fasciopathy

    Abstract

    Background

    Resistant plantar fasciopathy is a common orthopedic problem.

    Aim

    Comparing two different methods of treatment.

    Methods

    Fifty patients with chronic resistant plantar fasciopathy were divided into two groups. The first included 23 patients treated by endoscopic release of plantar fascia (EPF) and the second included 27 patients treated by injection of platelet-rich plasma (PRP).

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  • A study of autologous stem cells therapy assisted regeneration of cartilage in avascular bone necrosis

    Abstract

    Application of 'regenerative medicine' has given a new hope to surgeons for the treatment of several chronic diseases and disorders including severe orthopedic conditions. There are a myriad of orthopedic conditions and injuries that presently have limited therapeutic treatments and could benefit from new developing therapies in regenerative medicine with the help of stem cell therapy1. Regenerative medicine therapies are mainly based on the applications of stem cells. Stem cells play a vital role in orthopedic treatments and the studies have shown to have promising results in repair of bone, tendon, cartilage including avascular necrosis (AVN), spondylitis etc. Bone and cartilage regeneration ability of stem cells has been demonstrated clinically. However, success rate may not be same in every case and it depends on the patient profile. Several factors can be responsible for the same which include patient's immune response, the type and grade of the disease, which along with other confounding factors decide the outcome of the treatment. In this paper we have presented some of the orthopedic case studies performed through autologous transplantation of the stem cells.

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  • Platelet-Rich Plasma in Muscle Injuries: When and How It Can Be Used

    Abstract

    Presenting a significant problem in clinical medicine, skeletal muscle regeneration (after injuries, in atrophic disorders, etc.) is limited by fibrous scar formation, slow healing time, and a high rate of injury recurrence. Unfortunately, not many alternatives exist to the generally accepted conservative RICE principle for treating muscle injuries. Local platelet-rich plasma (PRP) application is popular in the field of sports medicine as an autologous source of growth factors that are believed to have potential therapeutic implications. However, several concerns have been raised as to whether high concentrations of TGF-β contained in PRP itself may have a negative effect in regard to fibrosis and the lack of any preclinical data. Although it is believed to be already used by many sports physicians, there is no evidence-based protocol for using PRP in treating muscle injuries. This chapter explains the reason behind it and proposes the best time frame to use PRP in muscle injuries according to physiological healing processes.

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  • The Effects of Prolotherapy With Hypertonic Dextrose Versus Prolozone (Intraarticular Ozone) in Patients With Knee Osteoarthritis

    Abstract

    Background: Knee osteoarthritis (KOA) is a common disabling disease. Limited studies have demonstrated that prolotherapy with dextrose or with prolozone can be helpful in the treatment of patients with KOA.

    Objectives: In the current study, we compared the results between these two treatment methods.

    Patients and Methods: In the current randomized clinical trial, 80 patients with mild to moderate KOA were randomly assigned equally into two groups (ozone group and dextrose group). In each group, injections were repeated three times with 10-day intervals. Before the treatment and 3 months after the injections, the pain intensity was measured by using a visual analogue scale and the Western Ontario and McMaster university arthritis index scores. Finally, the results were compared between the two groups.

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  • Comparison of the Cellular Composition and Cytokine-Release Kinetics of Various Platelet-Rich Plasma Preparations

    Abstract

    Background: Variations in formulations used to prepare platelet-rich plasmas (PRPs) result in differences in the cellular composition and biomolecular characteristics.

    Purpose: To evaluate the cellular composition and the cytokine-release kinetics of PRP according to differences in the preparation protocols.

    Study Design: Controlled laboratory study.

    Methods: Five preparation procedures were performed for 14 healthy subjects, including 2 manual procedures (single-spin [SS] at 900g for 5 minutes; double-spin [DS] at 900g for 5 minutes and then 1500g for 15 minutes) and 3 methods with commercial kits (Arthrex ACP, Biomet GPS, and Prodizen Prosys). After evaluation of cellular composition, each preparation was divided into 4 aliquots and incubated for 1 hour, 24 hours, 72 hours, and 7 days for the assessment of cytokine release over time. The cytokine-release kinetics were evaluated by assessing platelet-derived growth factor (PDGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), interleukin-1 (IL-1), and matrix metalloproteinase-9 (MMP-9) concentrations of each aliquot with bead-based sandwich immunoassay.

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  • Point-Counterpoint: Is PRP Beneficial For Chronic Plantar Fasciitis?

    Plantar fasciosis is heel pain caused by deterioration of the plantar fascia, which occurs as a result of repetitive stress and chronic plantar fasciitis. This is the term used for the non-inflamed phase of plantar fasciopathy. It is much more difficult to treat plantar fasciosis when healthcare providers fail to recognize it as the non-inflamed phase of the condition.

    In plantar fasciitis, there is adequate blood supply to the problematic area as well as an inflammatory response that happens to be painful. In plantar fasciosis, the fascia has a decreased or absent inflammatory response, a reduction in the growth/healing factors, and chronic scar tissue that prevents the healing process.

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  • Effectiveness and safety of prolotherapy injections for management of lower limb tendinopathy and fasciopathy: a systematic review

    Abstract

    Introduction

    The aim of this review was to identify and evaluate existing research to determine the clinical effectiveness and safety of prolotherapy injections for treatment of lower limb tendinopathy and fasciopathy.

    Review

    Nine databases were searched (Medline, Science Direct, AMED, Australian Medical Index, APAIS-Health, ATSIhealth, EMBASE, Web of Science, OneSearch) without language, publication or data restrictions for all relevant articles between January 1960 and September 2014. All prospective randomised and non-randomised trials, cohort studies, case-series, cross-sectional studies and controlled trials assessing the effectiveness of one or more prolotherapy injections for tendinopathy or fasciopathy at or below the superior aspect of the tibia/fibula were included. Methodological quality of studies was determined using a modified evaluation tool developed by the Cochrane Musculoskeletal Injuries Group. Data analysis was carried out to determine the mean change of outcome measure scores from baseline to final follow-up for trials with no comparative group, and for randomised controlled trials, standardised mean differences between intervention groups were calculated. Pooled SMD data were calculated where possible to determine the statistical heterogeneity and overall effect for short-, intermediate- and long-term data. Adverse events were also reported.

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  • Leukocyte-Reduced Platelet-Rich Plasma Normalizes Matrix Metabolism in Torn Human Rotator Cuff Tendons

    Abstract

    Background: The optimal platelet-rich plasma (PRP) for treatment of supraspinatus tendinopathy has not been determined.

    Purpose: To evaluate the effect of low- versus high-leukocyte concentrated PRP products on catabolic and anabolic mediators of matrix metabolism in diseased rotator cuff tendons.

    Study Design: Controlled laboratory study.

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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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