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  • Modulation of Hyaluronan Synthesis by the Interaction between Mesenchymal Stem Cells and Osteoarthritic Chondrocytes

    Abstract

    Bone marrow mesenchymal stem cells (BM-MSCs) are considered a good source for cellular therapy in cartilage repair. But, their potential to repair the extracellular matrix, in an osteoarthritic environment, is still controversial. In osteoarthritis (OA), anti-inflammatory action and extracellular matrix production are important steps for cartilage healing. This study examined the interaction of BM-MSC and OA-chondrocyte on the production of hyaluronan and inflammatory cytokines in a Transwell system. We compared cocultured BM-MSCs and OA-chondrocytes with the individually cultured controls (monocultures). There was a decrease in BM-MSCs cell count in coculture with OA-chondrocytes when compared to BM-MSCs alone. In monoculture, BM-MSCs produced higher amounts of hyaluronan than OA-chondrocytes and coculture of BM-MSCs with OA-chondrocytes increased hyaluronan production per cell. Hyaluronan synthase-1 mRNA expression was upregulated in BM-MSCs after coculture with OA-chondrocytes, whereas hyaluronidase-1 was downregulated. After coculture, lower IL-6 levels were detected in BM-MSCs compared with OA-chondrocytes. These results indicate that, in response to coculture with OA-chondrocytes, BM-MSCs change their behavior by increasing production of hyaluronan and decreasing inflammatory cytokines. Our results indicate that BM-MSCs per se could be a potential tool for OA regenerative therapy, exerting short-term effects on the local microenvironment even when cell:cell contact is not occurring.

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  • Low Oxygen Tension Enhances Osteogenic Potential of Bone Marrow-Derived Mesenchymal Stem Cells with Osteonecrosis-Related Functional Impairment

    Objective. Glucocorticoids can affect the function of bone marrow-derived mesenchymal stem cells (BMMSCs) adversely and merit the requirement for a strategy to correct this anomaly; we assessed the effect of low oxygen (2%) on BMMSCs from rabbits with osteonecrosis. Methods. Bone marrow-derived mesenchymal stem cells from normal rabbits and rabbits with osteonecrosis were divided into four groups: (1) normal-normoxia group, with normal BMMSCs cultured under 20% oxygen; (2) osteonecrosisnormoxia group, with BMMSCs fromrabbits with osteonecrosis cultured under 20% oxygen; (3) osteonecrosis-low oxygen treated group, with BMMSCs from rabbits with osteonecrosis cultured under 2% oxygen; (4) normal-low oxygen treated group, with normal BMMSCs cultured under 2% oxygen. The proliferation, osteogenic, and adipogenic differentiation ofMSCs and expression of stemness genes, osteogenic, and adipogenic differentiation markers were investigated. Results. Compared with BMMSCs from normal rabbits, those fromosteonecrosis rabbits showed significantly reduced proliferation ability, repressed expression of stemness genes, decreased osteoblasts formation, and increased adipocytes formation, indicating an osteonecrosis-related impairment. Low oxygen (2%) treated BMMSCs fromosteonecrosis rabbits showed not only increased proliferation and osteogenic potential but also decreased adipogenic potential. Conclusion. Low oxygen (2%) culture represents a novel strategy to augment BMMSC function affected by glucocorticoids and holds significance for future strategies to treat femoral head osteonecrosis.

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  • Case-control study on therapeutic effects of ozone and triamcinolone acetonide on the treatment of meniscal injury

    Abstract

    OBJECTIVE: To compare the clinical therapeutic effects between ozone and triamcinolone acetonide for the treatment of mild meniscal injury.

    METHODS: From January 2008 to December 2012, 119 patients with meniscal injury diagnosed as type I or II by MRI were divided into three groups. In the triamcinolone acetonide (A) group, there were 38 males and 2 females, with an average age of (25.34 +/- 6.34) years old, ranging from 18 to 48 years old; 36 patients had single knee injuries, 4 patients had double knee injuries and 44 knees with joint effusion. In the ozone (B) group,there were 37 males and 2 females, with an average age of (26.98 +/- 7.20) years old, ranging from 19 to 50 years old; 33 patients had single knee injuries, 6 patiens had double knees injuries and 40 knees with joint effusion. In the combination of ozone and triamcinolone acetonide (C) group, there were 37 males and 3 females,with an average age of (26.44 +/- 6.38) years old, ranging from 18 to 47 years old; 33 patients had single knee injuries, 7 patients had double knees injuries and 39 knees with joint effusion. The patients were treated with injection of 3 mg triamcinolone acetonide alone, 30 ml (30 microg/ml) ozone alone, or both two drugs respectively in knee joint cavity. All the treatment methods were carried out weekly and 4 times injections were required for a treatment course. Knee joint function was evaluated by Lysholm scale and knee joint effusion was examined by MRI before and after treatment.

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  • Management of Chronic Plantar Fasciitis using Hyperosmolar Dextrose Injection

    Abstract

    Plantar fasciitis is most common cause of heel pain. More than 90% of patients are managed by conservative treatment. Chronic recalcitrant cases of plantar fasciitis not responding to other treatment modalities can be managed by Hyperosmolar dextrose injections with no or minimal complications. Hyperosmolar dextrose injection has been shown to increase Beta-1 platelet derived growth factor expression and upregulation of multiple mitogenic factors that may act as signaling mechanisms in tissue repair. We recommend Hyperosmolar dextrose solution for the management of chronic plantar fasciitis in place of local corticosteroid injection, so as to avoid the complications like rupture of plantar fascia and fat pad atrophy which are associated with local corticosteroid injections.

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  • Intratendinous Injection of Platelet-Rich Plasma under US Guidance toTreat Tendinopathy:A Long- Term Pilot Study

    Abstract

    Purpose: To assess the potential therapeutic effect of intratendinous injection of platelet-richplasma(PRP) under ultrasound (US) guidance to treat tendon tears and tendinosis in a pilot study with long-term follow-up.

    Materials and Methods: The study included 408 consecutive patients referred fort reatment by PRP in jection of tendinopathy in the upper (medial and lateral epicondylar tendons)and the lower(patellar,Achilles,hamstring and adductor longus,and peroneal tendons)limb who received a single intra tendinous injection of PRP under US guidance. Clinical and US data were retrospectively collected for each anatomic compartment for upper and lower limbs before treatment(baseline)and 6 weeks after treatment. Late clinical data without US were collected until 32 months after the procedure(mean,20.2months). The McNemar test and regression model were used to compare clinical and US data.

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  • Platelet-rich Plasma as an Effective Treatment for Proximal Hamstring Injuries

    Abstract

    Proximal hamstring injuries can be disabling, and several traditional conservative treatments, including physiotherapy and nonsteroidal anti-inflammatory drugs, have been inconsistent. Corticosteroid injections have demonstrated success but can adversely affect local tissues. Platelet-rich plasma (PRP) has emerged as a safe, effective treatment for several orthopedic pathologies. The authors propose a PRP injection at the muscle origin as a novel treatment for proximal hamstring injuries.

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  • IL-6/STAT3 signaling pathway contributes to chondrogenic differentiation of human mesenchymal stem cells

    Abstract

    Objective: Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into chondrocytes. Articular cartilage contains MSC-like chondroprogenitor cells, suggesting their involvement in the maintenance of cartilage homeostasis by a self-repair mechanism. Interleukin (IL)-6 is a cytokine with a wide range of physiological functions, produced by MSCs in a steady manner and in large quantities. Thus, we investigated the involvement of IL-6 signaling in MSC differentiation into chondrocytes.

    Methods: Human bone marrow-derived MSCs were cultured by pellet culture system in a medium containing TGF-β3. Chondrogenic differentiation was detected by cartilage matrix accumulation and chondrogenic marker gene expression.

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  • Interactions between structural and chemical biomimetism in synthetic stem cell niches

    Abstract

    Advancements in understanding stem cell functions and differentiation are of key importance for the clinical success of stem-cell-based therapies. 3D structural niches fabricated by two-photon polymerization are a powerful platform for controlling stem cell growth and differentiation. In this paper, we investigate the possibility of further controlling stem cell fate by tuning the mechanical properties of such niches through coating with thin layers of biomimetic hyaluronan-based and gelatin-based hydrogels. We first assess the biocompatibility of chemical coatings and then study the interactions between structural and chemical biomimetism on the response of MSCs in terms of proliferation and differentiation. We observed a clear effect of the hydrogel coating on otherwise identical 3D scaffolds. In particular, in gelatin-coated niches we observed a stronger metabolic activity and commitment toward the osteo-chondral lineage with respect to hyaluronan-coated niches. Conversely, a reduction in the homing effect was observed in all the coated niches, especially in gelatin-coated niches. This study demonstrates the feasibility of controlling independently different mechanical cues, in bioengineered stem cell niches, i.e. the 3D scaffold geometry and the surface stiffness. This will allow, on the one hand, understanding their specific role in stem cell proliferation and differentiation and, on the other hand, finely tuning their synergistic effect.

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  • Evaluation of Cartilage Repair by Mesenchymal Stem Cells Seeded on a PEOT/PBT Scaffold in an Osteochondral Defect

    Abstract

    The main objective of this study was to evaluate the effectiveness of a mesenchymal stem cell (MSC)-seeded polyethylene-oxide-terephthalate/polybutylene-terephthalate (PEOT/PBT) scaffold for cartilage tissue repair in an osteochondral defect using a rabbit model. Material characterisation using scanning electron microscopy indicated that the scaffold had a 3D architecture characteristic of the additive manufacturing fabrication method, with a strut diameter of 296   ±  52  μm and a pore size of 512   ±  22  μm  ×—  476   ±  25  μm  ×—  180   ±  30  μm. In vitro optimisation revealed that the scaffold did not generate an adverse cell response, optimal cell loading conditions were achieved using 50  μg/ml fibronectin and a cell seeding density of 25  ×—  10(6)  cells/ml and glycosaminoglycan (GAG) accumulation after 28  days culture in the presence of TGFβ3 indicated positive chondrogenesis. Cell-seeded scaffolds were implanted in osteochondral defects for 12  weeks, with cell-free scaffolds and empty defects employed as controls. On examination of toluidine blue staining for chondrogenesis and GAG accumulation, both the empty defect and the cell-seeded scaffold appeared to promote repair. However, the empty defect and the cell-free scaffold stained positive for collagen type I or fibrocartilage, while the cell-seeded scaffold stained positive for collagen type II indicative of hyaline cartilage and was statistically better than the cell-free scaffold in the blinded histological evaluation. In summary, MSCs in combination with a 3D PEOT/PBT scaffold created a reparative environment for cartilage repair.

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  • Ultrasound-guided platelet-rich plasma injection for distal biceps tendinopathy

    Abstract

    Background Distal biceps tendinopathy is an uncommon cause of elbow pain. The optimum treatment for cases refractory to conservative treatment is unclear. Platelet-rich plasma has been used successfully for other tendinopathies around the elbow.

    Methods Six patients with clinical and radiological evidence of distal biceps tendinopathy underwent ultrasound-guided platelet-rich plasma (PRP) injection. Clinical examination findings, visual analogue score (VAS) for pain and Mayo Elbow Performance scores were recorded.

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  • Case-control study on local injection of autoallergic platelet rich plasma or whole blood for the treatment of tennis elbow

    Abstract

    OBJECTIVE: To compare therapeutic effects of local injection with autoallergic platelet rich plasma (PRP) or autoallergic whole blood (AWB) for the treatment of chronic tennis elbow.

    METHODS: From January 2011 to January 2014, 40 patients with chronic tennis elbow were divided into 2 groups, 20 cases in each group: PRP group and AWB group. There were 20 patients in PRP group treated with local injection of autoallergic platelet rich plasma, including 5 males and 15 females, with an average age of (47.50

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  • Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib

    Abstract

    Objectives To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.

    Methods

    Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0-500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D.

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  • Cell therapy in joint disorders

    Abstract

    CONTEXT: Articular cartilage possesses poor natural healing mechanisms, and a variety of non-cell-based and cell-based treatments aim to promote regeneration of hyaline cartilage.

    DATA SOURCES: A review of the literature to December 2013 using PubMed with search criteria including the keywords stem cell, cell therapy, cell transplantation, cartilage, chondral, and chondrogenic.

    STUDY SELECTION: Forty-five articles were identified that employed local mesenchymal stem cell (MSC) therapy for joint disorders in humans. Nine comparative studies were identified, consisting of 3 randomized trials, 5 cohort studies, and 1 case-control study.

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  • Intra-articular injection of mesenchymal stem cells leads to reduced inflammation and cartilage damage in murine antigen-induced arthritis

    Abstract

    BACKGROUND: Rheumatoid arthritis (RA) is a debilitating and painful disease leading to increased morbidity and mortality and novel therapeutic approaches are needed. The purpose of this study was to elucidate if mesenchymal stem cells (MSCs) injected in the joints of mice with arthritis are therapeutic, reducing joint swelling and cartilage destruction.

    METHODS: Murine mesenchymal stem cells (mMSCs) were isolated from bone marrow of C57Bl/6 mice and expanded in culture. Cells were tested for immunophenotype and their ability to form colonies and to differentiate into chondrocytes, osteocytes and adipocytes. Antigen-induced arthritis (AIA) was induced by intra-articular injection of methylated bovine serum albumin into the knee joints of preimmunized C57Bl/6 mice. After one day, when peak swelling occurs, 500,000 mMSCs labelled with red fluorescent cell tracker CM-DiI were injected intra-articularly in the right knee joint. Left knee joints were treated as controls by receiving PBS injections. Differences between groups were calculated by Mann Whitney U test or unpaired t tests using GraphPad Prism software version 5.

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  • In situ recruitment of human BMSCs using chemokines for articular cartilage regeneration

    Abstract

    Bone marrow-derived mesenchymal stem cells (BMSCs) are a good cell source for regeneration of cartilage as they can migrate directly to the site of cartilage injury and differentiate into articular chondrocytes. Articular cartilage defects do not heal completely due to the lack of chondrocytes or BMSCs at the site of injury. In this study, the chemotaxis of BMSCs toward chemokines, which may give rise to a complete regeneration of the articular cartilage, was investigated. CCR2, CCR4, CCR6, CXCR1, and CXCR2 were expressed in normal BMSCs and were increased significantly upon treatment with pro-inflammatory cytokines. BMSC migration was increased by MIP-3a and IL-8 more than by MCP-1 or SDF-1?. IL-8 and MIP-3? significantly enhanced the chemotaxis of BMSCs compared with MCP-1, SDF-1?, or the PBS. Human BMSC recruitment to transplanted scaffolds containing either IL-8 or MIP-3? significantly increased in vivo compared with that to scaffolds containing the PBS. Furthermore, IL-8- and MIP-3?-containing scaffolds enhanced tissue regeneration of ostechondral defect site formed in beagle knee articular cartilage. Therefore, this study suggests that IL-8 and MIP-3? are the candidates that induce the regeneration of damaged articular cartilage.

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  • Surgery for persistent knee pain? Not so fast

    Illustrative case

    A 40-year-old man comes to your office for follow-up of medial left knee pain he\'s had for 3 months that hasn\'t responded to conservative treatment. The pain developed gradually, without a history of trauma. The patient has no signs of degenerative joint disease on x-ray but magnetic resonance imaging (MRI) reveals a tear of the medial meniscus. Should you refer him for meniscectomy?

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  • Stromal cells and stem cells in clinical bone regeneration

    Abstract

    Stem-cell-mediated bone repair has been used in clinical trials for the regeneration of large craniomaxillofacial defects, to slow the process of bone degeneration in patients with osteonecrosis of the femoral head and for prophylactic treatment of distal tibial fractures. Successful regenerative outcomes in these investigations have provided a solid foundation for wider use of stromal cells in skeletal repair therapy. However, employing stromal cells to facilitate or enhance bone repair is far from being adopted into clinical practice. Scientific, technical, practical and regulatory obstacles prevent the widespread therapeutic use of stromal cells. Ironically, one of the major challenges lies in the limited understanding of the mechanisms via which transplanted cells mediate regeneration. Animal models have been used to provide insight, but these models largely fail to reproduce the nuances of human diseases and bone defects. Consequently, the development of targeted approaches to optimize cell-mediated outcomes is difficult. In this Review, we highlight the successes and challenges reported in several clinical trials that involved the use of bone-marrow-derived mesenchymal or adipose-tissue-derived stromal cells. We identify several obstacles blocking the mainstream use of stromal cells to enhance skeletal repair and highlight technological innovations or areas in which novel techniques might be particularly fruitful in continuing to advance the field of skeletal regenerative medicine.

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  • Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis

    Abstract

    Objectives: To determine and compare the effects of autologous platelet rich plasma (PRP) and hyaluronic acid (HA) for the treatment of osteoarthritis of the knee.

    Methods: This prospective study included 150 patients affected by severe osteoarthritis of the knee. Gonarthrosis was graded using the Kellgren-Lawrence and Albhack radiographic classification scale. 150 patients were randomized into 2 study groups .In the PRP group (n=55) three intraarticular injection were applied andthe control group (n=55) received 3 intra-articular injections of high molecular weight HA. An unblinded physician performed infiltration once a week for 3 weeks into the knee affected by clinically relevant gonarthrosis (in both groups). All patients were evaluated with the Western Ontario and McMaster (WOMAC) score and visual pain scale before the infiltration and at 3, 6, and 12 months after the first injection.

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  • Matrix-Induced Autologous Chondrocyte Implantation versus Multipotent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions A Nonrandomized Prospective Trial

    Abstract

    Objective. To compare the outcome of matrix-induced autologous chondrocyte implantation (MACI) and bone marrow aspirate concentrate (BMAC)-derived multipotent stem cells (MSCs) implantation in patellofemoral chondral lesions, using the same HYAFF11 scaffold. Methods. From January 2005 to December 2010, 37 patients with patellofemoral chondral lesions were prospectively followed up, for a minimum of 3 years; 19 of these patients were treated with MACI and 18 with BMAC. Radiographs, magnetic resonance imaging, and clinical scores (International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, visual analog scale, and Tegner) were collected preoperatively, at 2-year and final follow-up. Five patients of MACI and 6 of the BMAC group underwent second-look arthroscopy; 4 patients of each group consented to a concomitant biopsy. Results. No adverse reactions or postoperative infections were noted. Baseline characteristics were similar in both groups (P > 0.05). Both groups showed significant improvement in all scores, from preoperative to final follow-up (P = 0.001), but there was no significant difference in improvement between the 2 groups, except for the IKDC subjective score (P = 0.015), which favored the BMAC group. Deterioration in MACI and improvement in BMAC group scores were noticed, from 2-year to final follow-up, but was nonsignificant. MACI patients with trochlear lesions showed better results than patellar lesions, while location was not a prognostic factor in the BMAC group. MRI showed complete filling of the defects in 76% of patients in MACI and 81% of patients in BMAC, and histological analysis revealed hyaline-like features. Conclusion. Both techniques are viable and effective for large patellofemoral chondral lesions at minimum 3-year follow-up.

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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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