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  • Mesenchymal Stem Cells and Cartilage Regeneration in Traumatic and OsteoarthriticCartilage Defects

    Abstract

    Osteoarthritis (OA) affects several hundred million people and is one of the leading causes of disability around the world. Aging is the most influential risk factor for developing OA. Cartilage has a limited ability to spontaneously heal; therefore, it needs surgical intervention in case of cartilage defects caused by traumatic injury or degenerative disease. Due to the shortage of autologous chondrocytes and autografts that require additional defects, adult human mesenchymal stem cells (MSCs), the precursors of chondrocytes, become possible options for cartilage regeneration in traumatic and Osteoarthritic cartilage defects.

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  • The effects of repeated intra-articular PRP injections on clinical outcomes of early osteoarthritis of the knee

    Abstract

    Purpose To assess the outcome of intra-articular plateletrich plasma (PRP) injections into the knee in patients with early stages of osteoarthritis (OA) and to determine whether cyclical dosing would affect the end result. Methods This is a prospective, randomized study in which 93 patients (119 knees) were followed up for a minimum of 2 years. Fifty knees were randomly selected prior to the first injection, to receive a second cycle at the completion of 1 year. A cycle consisted of three injections, each given at a monthly interval. The outcome was assessed using Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual Analogue Scale (VAS), Tegner and Marx scoring systems, recorded prior to the first injection and then at 12, 18 and 24 months.

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  • Tendon Derived Stem Cells Promote Platelet-Rich Plasma Healing in Collagenase-Induced Rat Achilles Tendinopathy

    Abstract

    Background/Aims: Tendon injuries are common, difficult to cure and usually healed with fibrosis and scar tissue. The aim of this study was to evaluate tendon derived stem cells (TDSCs) and platelet rich plasma (PRP) in the treatment of collagenase induced Achilles tendinopathy in rat. Methods: Four and 8 weeks (n=18) after TDSCs, PRP, PRP with TDSC or PBS (control) injection into collagenase or saline (sham) injected rat Achilles tendon, tendon tissue was harvested and tendon quality was evaluated by histology and biomechanical testing. TDSCs were cultured and treated by 10% PRP, and the FAK/ERK1/2 signaling pathway and tenocyte-related genes were detected by western blot analysis. Results: Compared to the control, PRP treatment resulted in better healing of injured tendons with improved histological outcomes and biomechanical functions. The addition of TDSCs to PRP treatment significantly enhanced the effects of PRP treatment alone. TDSC injection alone had little effect on tendon healing. PRP and PRP with TDSC treatments of collagenase induced tendon injuries also increased the mRNA and protein expression of tenocyte-related genes (type I collagen, SCX, Tenascin C) and activated the focal adhesion kinase (FAK) and extracellular-regulated kinase (ERK) 1/2 signaling pathways. Treatment of TDSCs in vitro with 10% PRP significantly increased the phosphorylation levels of FAK and ERK1/2 and the protein levels of tenocyte-related genes (Col I, SCX and Tenascin C). Inhibition of the FAK and ERK1/2 signaling pathways abolished the effect of PRP. Conclusion: This study concludes that PRP combined with TDSCs is potentially effective for the treatment of tendinopathy. The PRP induced, FAK and ERK1/2 dependent activation of tenocyte related genes in TDSCs in vitro suggests that the beneficial healing effect of the PRP with TDSC combination might occur by means of an improved TDSC differentiation toward the tenocyte lineage. Thus, a PRP with TDSC combination therapy may be clinically useful.

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  • Oxygen-ozone therapy for herniated lumbar disc in patients with subacute partial motor weakness due to nerve root compression

    Abstract

    Intradiscal oxygen-ozone (O2-O3) chemonucleolysis is a well-known effective treatment for pain caused by protruding disc disease and nerve root compression due to bulging or herniated disc. The most widely used therapeutic combination is intradiscal injection of an O2-O3 mixture (chemonucleolysis), followed by periradicular injection of O2-O3, steroid and local anaesthetic to enhance the anti-inflammatory and analgesic effect. The treatment is designed to resolve pain and is administered to patients without motor weakness, whereas patients with acute paralysis caused by nerve root compression undergo surgery 24-48h after the onset of neurological deficit. This paper reports on the efficacy of O2-O3 chemonucleolysis associated with anti-inflammatory foraminal injection in 13 patients with low back pain and cruralgia, low back pain and sciatica and subacute partial motor weakness caused by nerve root compression unresponsive to medical treatment. All patients were managed in conjunction with our colleagues in the Neurosurgery Unit of Bellaria Hospital and the IRCCS Institute of Neurological Sciences, Bologna. The outcomes obtained are promising: 100% patients had a resolution of motor weakness, while 84.6% had complete pain relief. Our results demonstrate that O2-O3 therapy can be considered a valid treatment option for this category of patients.

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  • Single injection of platelet-rich plasma (PRP) for the treatment of refractory distal biceps tendonitis: long-term results of a prospective multicenter cohort study

    Abstract

    Purpose

    There is a lack of evidence regarding the use of PRP in the treatment of distal biceps tendonitis. The purpose of this study was to assess the effectiveness of ultrasound (US)-guided injection of PRP in relieving pain and functional impairment in the treatment of refractory distal biceps tendonitis.

    Methods

    Twelve patients from two large tertiary referral hospitals were recruited over a period of 20

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  • Single Dose of Intra-Muscular Platlet Rich Plasma Reverses the Increase in Plasma Iron Levels in Exercise Induced Muscle Damage

    Abstract

    Objectives: Autologous Platelet Rich Plasma (PRP) therapy, is considered to be a promising solution in accelerating the healing process of injured skeletal muscle tissue. In addition to the release of growth factors, PRP also promotes concentrated anti-inflammatory signals, including interleukins. However, the impact of the intramuscular administration of the PRP on hematologic and biochemical responses has not been fully elucidated in exercise induced muscle damage.

    Methods: Twelve healthy moderately active male volunteers, without previous experience with eccentric/concentric elbow flexors exercise, participated in this study. They were divided into two groups: control group (CONTROL, n=6) and platelet rich plasma administration group (PRP, n=6) group. To induce muscle damage, subjects in both groups performed concentric/eccentric contractions with load of (80 % 1RM) maximal voluntary contraction of the elbow flexors until point of exhaustion of the non-dominant arm. The non-dominant arms of the PRP group were treated with autologous PRP (Regen ACR-C, Regen Lab, Switzerland) post-24h exercise induced damage (DOMS). Subsequently, 4 ml PRP samples was injected using a 20-gauge needle into the region of the biceps brachii of the non-dominant arm under sterile aseptic conditions. Venous blood samples were collected pre-, and 4 days post-exercise, and analyzed for complete blood counts, serum ferritin, iron, iron binding capacity (IBC), creatinine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT) as markers of muscle damage and inflammation.

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  • Fibroblast Growth Factor 18 Increases the Trophic Effects of Bone Marrow Mesenchymal Stem Cells on Chondrocytes Isolated from Late Stage Osteoarthritic Patients

    1. Introduction

    Osteoarthritis (OA) is known as the most common degenerative diseases in joints. Symptoms of OA include a group of mechanical abnormalities, which reflect the degradationof articular cartilage and the corresponding subchondral bones [1]. OA patients normally experience pain, tenderness, stiffness, locking, and/or effusion of joints. A lot of factorsincluding genetics, developmental environment,metabolism, and mechanical injury are considered as causes for initiating degradation of cartilage. Once started, cartilage tissue willbecome thinner and thinner; then bony surfaces of joints will be protected and buffer less and less. Then subchondral bone may be damaged. As the most common type of arthritis, to be an anabolic factor on chondrocytes in articular cartilage [10]. It has also been reported that FGF18 may accelerate the biosynthesis of type II collagen synthesis and extracellular matrix deposition of chondrocytes [11]. Based on these reports as well as the fact that injection of rhFGF18 prevented cartilage degeneration in rat osteoarthritis models, FGF18 is believed to protect articular cartilage from intra-articular injury [12]. Furthermore, beneficial effects of FGF18 have also been shown in the repair of damaged cartilage in a rat study of injury-induced osteoarthritis, conducted by Moore et al. [13].

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  • Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration

    Abstract

    The aims of this study were to (1) determine whether platelet-rich plasma (PRP) could be prepared as a bioactive scaffold capable of endogenous growth factor release for cartilage repair; (2) compare the chondrogenic differentiation ability of mesenchymal stem cells (MSCs) from bone marrow (BMSC) and from adipose (ADSC) seeded within the PRP scaffold; and (3) test the efficacy of ADSC-PRP construct in cartilage regeneration in

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  • Efficacy of platelet-rich plasma injections in osteoarthritis of the knee: a systematic review and meta-analysis

    Abstract

    Background The effectiveness of platelet-rich plasma (PRP) injections for osteoarthritis (OA) is still controversial. We investigated the effect of PRP injections in patients with knee OA based on decreasing pain, improving function, global assessment and changes regarding joint imaging.

    Methods We performed a comprehensive, systematic literature search in computerised databases (MEDLINE, EMBASE, CINAHL, CENTRAL, Web of Science and PEDro) until June 2014 for randomised or non-randomised controlled trials. These were graded for risk of bias and a level of evidence was provided. If possible, meta-analysis was performed

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  • Role of platelet-rich plasma in articular cartilage lesions

    Articular cartilage has only a limited capacity of selfhealing. Once seriously damaged, articular cartilage lesions will not regenerate; and any joint surface damage,if left untreated, will invariably deteriorate and eventually spread to surrounding areas.1 The end result of such a process is often the development of osteoarthritis (OA),which often occurs in large load-bearing joints, such as knee and femoral joint. So much attention has been focused on how to eliminate symptoms, repair damaged cartilage,restore the integrity of the articular surface, prevent or halt joint degeneration, and improve joint function. But it still remains a challenging problem for orthopedic surgeons.In recent years, the role of growth factors (GFs) on tissue repair has become a hot research topic. The biological effect of GFs on cartilage repair has been well documentedin vivo and in vitro.2-4 At present, most GFs are obtained mainly through genetic engineering technology and extracted from the animals; the preparation process is cumbersome, expensive, and inconvenient.

    Articular cartilage has only a limited capacity of selfhealing. Once seriously damaged, articular cartilage lesions will not regenerate; and any joint surface damage, if left untreated, will invariably deteriorate and eventually spread to surrounding areas.1 The end result of such a process is often the development of osteoarthritis (OA), which often occurs in large load-bearing joints, such as knee and femoral joint. So much attention has been focused on how to eliminate symptoms, repair damaged cartilage, restore the integrity of the articular surface, prevent or halt joint degeneration, and improve joint function. But it still remains a challenging problem for orthopedic surgeons. In recent years, the role of growth factors (GFs) on tissue repair has become a hot research topic. The biological effect of GFs on cartilage repair has been well documented in vivo and in vitro.2-4 At present, most GFs are obtained mainly through genetic engineering technology and extracted from the animals; the preparation process is cumbersome, expensive, and inconvenient.

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  • Effect of two different preparations of platelet-rich plasma on synoviocytes

    Abstract

    Purpose: To analyse the modifications induced by two different platelet-rich plasma (PRP) preparations on osteoarthritis (OA) synoviocytes, by documenting changes in gene expression of factors involved in joint physiopathology.

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  • Platelet rich plasma enhances the immunohistochemical expression of platelet derived growth factor and vascular endothelial growth factor in the synovium of the meniscectomized rat models of osteoarthritis

    Abstract

    This study was carried out on a rat model of surgically-induced osteoarthritis (OA) to assess the histological and immunohistochemical changes in the synovial membrane and to evaluate the effects of intra-articular injection of platelet rich plasma (PRP) in such cases. Forty five male albino rats were divided into 3 equal groups; control, surgically-induced OA and surgically-induced OA followed by intra-articular injection of PRP. Knee joints were processed for histological and immunohistochemical staining with anti-platelet derived growth factor (PDGF-A) and anti-vascular endothelial growth factor (VEGF) and the area percentages of immunostaining were measured by digital image analysis. Serum levels of PDGF-A and VEGF were analyzed by ELISA. The osteoarthritis research society international (OARSI) score was significantly higher in OA (2433.8

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  • Effects of anti-aggregant, anti-inflammatory and anti-coagulant drug consumption on the preparation and therapeutic potential of plasma rich in growth factors (PRGF)

    Abstract

    The prevalence and incidence of trauma-related injuries, coronary heart disease and other chronic diseases increase dramatically with age. This population sector is therefore a regular consumer of different types of drugs that may affect platelet aggregation and the coagulation cascade. We have evaluated whether the consumption of acetylsalicylic acid, acenocoumarol, glucosamine sulfate and chondroitin sulfate, and therefore their presence in blood, could interfere with the preparation and biological outcomes of plasma rich in growth factors (PRGF). Clotting time, clot retraction and platelet activation of PRGF was evaluated. PRGF growth factor content and the release of different biomolecules by tendon fibroblasts were also quantified, as well as cell proliferation and cell migration. The preparation and biological potential of PRGF is not affected by the intake of the evaluated drugs, and solely its angiogenic potential and its capacity to induce HA and fibronectin synthesis, is reduced in patients taking anti-coagulants.

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  • USE OF PLATELET-RICH PLASMA INJECTION FOR THE TREATMENT OF CHRONIC PLANTAR FASCITIS

    Abstract

    Plantar fascitis is a common cause of heel pain and different treatment options exists. PRP (platelet rich plasma) derived from autologous blood containing high concentration of growth factors help in tissue healing. The use of PRP in the treatment of plantar fascitis is fairly recent an evolving concept. The purpose of our work was to study the effectiveness of PRP in the treatment of chronic plantar fascitis.

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  • Dwight Howard out indefinitely

    HOUSTON -- There is no timetable for Houston Rockets center Dwight Howard\'s return after he underwent platelet-rich plasma therapy to treat his strained right knee, coach Kevin McHale said before Saturday night\'s 95-92 win against the Dallas Mavericks.

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  • TGF-β1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells

    Replacement of degenerated cartilage with cell-based cartilage products may offer a long-term solution to halt arthritis\' degenerative progression. Chondrocytes are frequently employed in cell-based FDA-approved cartilage products, yet human marrow-derived stromal cells (hMSCs) show significant translational potential, reducing donor site morbidity and maintaining their undifferentiated phenotype with expansion. This study sought to investigate the effects of transforming growth factor β1 (TGF-β1), growth/differentiation factor 5 (GDF-5), and bone morphogenetic protein 2 (BMP-2) during post-expansion chondrogenesis in human articular chondrocytes (hACs) and to compare chondrogenesis in passaged hACs with that of passaged hMSCs. Through serial expansion, chondrocytes dedifferentiated, decreasing expression of chondrogenic genes while increasing expression of fibroblastic genes. However, following expansion, 10 ng/mL TGF-β1, 100 ng/mL GDF-5, or 100 ng/mL BMP-2 supplementation during three-dimensional aggregate culture each upregulated one or more markers of chondrogenic gene expression in both hACs and hMSCs. Additionally, in both cell types, the combination of TGF-β1, GDF-5, and BMP-2 induced the greatest upregulation of chondrogenic genes, i.e., Col2A1, Col2A1/Col1A1 ratio, SOX9, and ACAN, and synthesis of cartilage-specific matrix, i.e., glycosaminoglycans (GAGs) and ratio of collagen II/I. Finally, TGF-β1, GDF-5, and BMP-2 stimulation yielded mechanically robust cartilage rich in collagen II and GAGs in both cell types, following 4 wks maturation. The present study illustrates notable success in employing the self-assembling method to generate robust, scaffold-free neocartilage constructs using expanded human ACs and MSCs. Stem Cells 2014

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  • Cartilage Oligomeric Matrix Protein Gene Multilayers Inhibit Osteogenic Differentiation and Promote Chondrogenic Differentiation of Mesenchymal Stem Cells

    Abstract

    There are still many challenges to acquire the optimal integration of biomedical materials with the surrounding tissues. Gene coatings on the surface of biomaterials may offer an effective approach to solve the problem. In order to investigate the gene multilayers mediated differentiation of mesenchymal stem cells (MSCs), gene functionalized films of hyaluronic acid (HA) and lipid-DNA complex (LDc) encoding cartilage oligomeric matrix protein (COMP) were constructed in this study via the layer-by-layer self-assembly technique. Characterizations of the HA/DNA multilayered films indicated the successful build-up process. Cells could be directly transfected by gene films and a higher expression could be obtained with the increasing bilayer number. The multilayered films were stable for a long period and DNA could be easily released in an enzymatic condition. Real-time polymerase chain reaction (RT-PCR) assay presented significantly higher (p < 0.01) COMP expression of MSCs cultured with HA/COMP multilayered films. Compared with control groups, the osteogenic gene expression levels of MSCs with HA/COMP multilayered films were down-regulated while the chondrogenic gene expression levels were up-regulated. Similarly, the alkaline phosphatase (ALP) staining and Alizarin red S staining of MSCs with HA/COMP films were weakened while the alcian blue staining was enhanced. These results demonstrated that HA/COMP multilayered films could inhibit osteogenic differentiation and promote chondrogenic differentiation of MSCs, which might provide new insight for physiological ligament-bone healing.

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  • Simultaneous regeneration of full-thickness cartilage and subchondral bone defects in vivo using a three-dimensional scaffold-free autologous construct derived from high-density bone marrow-derived mesenchymal stem cells

    Abstract

    BackgroundIn recent years, several methods have been developed for repairing full-thickness cartilage defects by tissue engineering using mesenchymal stem cells. Most of these use scaffolds to achieve sufficient thickness. However, considering the potential influence of scaffolds on the surrounding microenvironment, as well as immunological issues, it is desirable to develop a scaffold-free technique. In this study, we developed a novel technique, a scaffold-free autologous construct derived from bone marrow-derived mesenchymal stem cells (BM-MSCs), and successfully use this technique to regenerate cartilage and subchondral bone to repair an osteochondral defect in rabbit knees.MethodsBM-MSCs were isolated from bone marrow liquid aspirated from the iliac crest of rabbits. After expansion in culture dishes and re-suspension in 96-well plates, the cells spontaneously aggregated into a spheroid-like structure. The spheroids were loaded into a tube-shaped Teflon mold with a 5-mm height and maintained under air-liquid interface conditions. These loaded spheroids fused with each other, resulting in a cylinder-shaped construct made of fused cells that conformed to the inner shape of the mold. The construct was implanted into an osteochondral defect in rabbit knees and histologically analyzed 24 and 52

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  • Platelet derived growth factor (PDGF) contained in Platelet Rich Plasma (PRP) stimulates migration of osteoblasts by reorganizing actin cytoskeleton

    Abstract

    Platelet-rich plasma (PRP) is a platelet concentrate in a small volume of plasma. It is highly enriched in growth factors able to stimulate the migration and growth of bone-forming cells. PRP is often used in clinical applications, as dental surgery and fracture healing. Platelet derived growth factor (PDGF), is highly concentrated in PRP and it was shown in our previous studies to provide the chemotactic stimulus to SaOS-2 osteoblasts to move in a microchemotaxis assay. Aim of the present studies is to analyze the effects of a PRP pretreatment (short time course: 30-150

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  • The Lipid Portion of Activated Platelet-Rich Plasma Significantly Contributes to Its Wound Healing Properties

    Abstract

    Objective: Platelet-rich plasma (PRP) is a popular choice for the treatment of chronic wounds. Current dogma attributes these healing properties to the peptide growth factors of PRP. However, PRP is also rich in bioactive lipids whose contribution to healing has not been characterized and warrants investigation due to the protease-rich environment of chronic wounds.

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