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  • Histochemical and Functional Improvement of Adipose-Derived Stem Cell-Based Tissue-Engineered Cartilage by Hyperbaric Oxygen/Air Treatment in a Rabbit Articular Defect Model

    Cartilage is exposed to compression forces during joint loading. Therefore, exogenous stimuli are frequently used in cartilage tissue engineering strategies to enhance chondrocyte differentiation and extracellular matrix (ECM) secretion. In this study, human adipose-derived stem cells were seeded on a gelatin/polycaprolactone scaffold to evaluate the histochemical and functional improvement of tissue-engineered cartilage after hyperbaric oxygen/air treatment in a rabbit articular defect model. Behavior tests showed beneficial effects on weight-bearing and rear leg-supporting capacities after treatment of tissue-engineered cartilage with 2.5 ATA oxygen or air. Moreover, positron emission tomography images and immunohistochemistry staining demonstrated hydroxyapatite formation and increased ECM synthesis, respectively, at the tissue-engineered cartilage graft site after high pressure oxygen/air treatment. Based on these results, we concluded that hyperbaric oxygen and air treatment can improve the quality of tissue-engineered cartilage in vivo by increasing the synthesis of ECM.

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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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  • Platelet-rich Plasma Modulates the Secretion of Inflammatory/Angiogenic Proteins by Inflamed Tenocytes

    Abstract

    BACKGROUND: Platelet-rich plasma therapies for tendinopathy appear to provide moderate pain reduction. However, the biological mechanisms behind the observed clinical effects remain poorly characterized. QUESTIONS

    PURPOSES: The purpose of this study was to explore whether platelet-rich plasma modifies the inflammatory/angiogenic status of already inflamed tenocytes by examining (1) gene expression; (2) modulation of chemokine and interleukin secretion; and (3) differences between healthy and tendinopathic tenocytes.

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  • Platelet-rich plasma to treat ankle cartilage pathology - from translational potential to clinical evidence: a systematic review

    Abstract

    Platelet-rich Plasma (PRP) is a fascinating biological treatment showing promising results for the management of cartilage disorders. However, despite the step forwards in this research area and the increasing use of PRP in clinical practice, its use remains still controversial and especially its application as injective treatment for ankle cartilage pathology have been scarcely investigated.

    The aim of this paper is to describe the translational evidence for the use of PRP in cartilage treatment and to systematically review all the available evidence regarding the clinical application of PRP for ankle cartilage disorders, in order to understand what is the current state of the art for this specific clinical indication, underlining both limits and potential of this biological strategy.

    A systematic review of the clinical literature was performed on the use of PRP to treat ankle cartilage disorders and 7 papers were identified. PRP has been used in two different ways: 5 of the available papers focus on its use as an augmentation procedure to various surgical techniques for cartilage regeneration, while only two studies report its conservative application through intra-articular injections. Based on the limited number of clinical studies available on this topic, this systematic review showed the lack of major adverse events related to PRP and overall good results for the treatment of ankle cartilage pathology, thus confirming the translational potential of this biological treatment suggested by several preclinical studies. Further high quality clinical trials in the ankle are still needed to clarify proper indications and best applicative modalities.

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

    Abstract

    Plantar fasciitis is the most common cause of heel pain which seems difficult to treat in its most chronic and severe forms. Earlier treatments, including orthoses, non steroidal anti-inflammatory drugs, and steroid injections are paucity of supportive clinical evidence but carry the potential for serious

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  • Mesenchymal stromal cells and rheumatic diseases: new tools from pathogenesis to regenerative therapies

    Abstract

    In recent years, mesenchymal stromal cells (MSCs) have been largely investigated and tested as a new therapeutic tool for several clinical applications, including the treatment of different rheumatic diseases. MSCs are responsible for the normal turnover and maintenance of adult mesenchymal tissues as the result of their multipotent differentiation abilities and their secretion of a variety of cytokines and growth factors. Although initially derived from bone marrow, MSCs are present in many different tissues such as many peri-articular tissues. MSCs may exert immune-modulatory properties, modulating different immune cells in both in

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  • New and Emerging Strategies in Platelet-Rich Plasma Application in Musculoskeletal Regenerative Procedures: General Overview on Still Open Questions and Outlook

    Abstract

    Despite its pervasive use, the clinical efficacy of platelet-rich plasma (PRP) therapy and the different mechanisms of action have yet to be established. This overview of the literature is focused on the role of PRP in bone, tendon, cartilage, and ligament tissue regeneration considering basic science literature deriving from in vitro and in vivo studies. Although this work provides evidence that numerous preclinical studies published within the last 10 years showed promising results concerning the application of PRP, many key questions remain unanswered and controversial results have arisen. Additional preclinical studies are needed to define the dosing, timing, and frequency of PRP injections, different techniques for delivery and location of delivery, optimal physiologic conditions for injections, and the concomitant use of recombinant proteins, cytokines, additional growth factors, biological scaffolds, and stems cells to develop optimal treatment protocols that can effectively treat various musculoskeletal conditions.

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  • Systemic and local administration of allogeneic bone marrow derived mesenchymal stem cells promotes fracture healing in rats

    Abstract

    Mesenchymal stem cells (MSCs) are immune-privileged and a cell source for tissue repair. Previous studies showed that there is systemic mobilization of osteoblastic precursors to the fracture site, we hypothesized that both systemic and local administration of allogeneic MSCs may promote fracture healing. Bone marrow derived MSCs and skin fibroblasts were isolated from the GFP-Sprague-Dawley rats, cultured and characterized. Closed transverse femoral fracture with internal fixation was established in 48 adult male Sprague-Dawley rats, whom were randomly assigned into 4 groups receiving: PBS injection; MSCs systemic injection; Fibroblasts systemic injection and MSCs fracture site injection. 2x106 cells were injected at 4 days after fracture. All animals were terminated at 5 weeks after fracture; examinations included weekly radiograph; Micro-CT; mechanical testing; histology, immunohistochemistry and double immunofluorescence. The callus size of MSCs injection groups were significant larger among all the groups. Radiographs and 3D-reconstruction images showed that the fracture gaps united in the MSCs injected groups, while gaps were still seen in the fibroblast and PBS injection groups. The mechanical properties were significantly higher in the MSCs injection groups than those in the fibroblast and PBS groups, but no difference was found between the MSCs local and systemic injection groups. Immunohistochemistry and double immunofluorescence demonstrated that GFP-positive MSCs were present in the callus in the MSCs injection groups at 5 weeks after fracture, and some have differentiated into osteoblasts. Quantitative analysis revealed the number of GFP-positive cells in the callus in the MSCs systemic injection group was significantly lower than that of the MSCs local injection group. The proportion of GFP-osteoblasts in GFP-positive cells in the MSCs systemic injection group was significantly lower than that of the MSCs local injection group. These findings provide critical insight for developing MSC-based therapies and systemic injection of allogeneic MSCs may be a novel treatment method for promoting fracture repair.

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  • Regenerative treatment in osteochondral lesions of the talus: autologous chondrocyte implantation versus one-step bone marrow derived cells transplantation

    Abstract

    Purpose

    Osteochondral lesions of the talus (OLT) usually require surgical treatment. Regenerative techniques for hyaline cartilage restoration, like autologous chondrocytes implantation (ACI) or bone marrow derived cells transplantation (BMDCT), should be preferred. The aim of this work is comparing two clusters with OLT, treated with ACI or BMDCT.

    Methods

    Eighty patients were treated with regenerative techniques, 40 with ACI and 40 with BMDCT. The two groups were homogenous regarding age, lesion size and depth, previous surgeries, etiology of the lesion, subchondral bone graft, final follow-up and pre-operative AOFAS score. The two procedures were performed arthroscopically. The scaffold was a hyaluronic acid membrane in all the cases, loaded with previously cultured chondrocytes (ACI) or with bone marrow concentrated cells, harvested in the same surgical session (BMDCT). All the patients were clinically and radiologically evaluated, using MRI Mocart score and T2 mapping sequence.

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  • Differentiation of directly co-cultured bone marrow mesenchymal stem cells and ligament fibroblasts into ligament cells after induced by transforming growth factor β1 and basic fibroblast growth factor

    Abstract

    OBJECTIVE: To investigate the effect of transforming growth factor β1 (TGF-β1) and basic fibroblast growth factor 1 (bFGF-1) on the cellular activities, proliferation, and expressions of ligament-specific mRNA and proteins in bone marrow mesenchymal stem cells (BMSCs) and ligament fibroblasts (LFs) after directly co-cultured.

    METHODS: BMSCs from 3-month-old Sprague Dawley rats were isolated and cultured using intensity gradient centrifugation. LFs were isolated using collagenase. The cells at passage 3 were divided into 6 groups: non-induced BMSCs group (group A), non-induced LFs group (group B), non-induced co-cultured BMSCs and LFs group (group C), induced BMSCs group (group D), induced LFs group (group E), and induced co-cultured BMSCs and LFs group (group F). The cellular activities and proliferation were examined by inverted contrast microscope and MTT; the concentrations of collagen type I and type III were determined by ELISA; and mRNA expressions of collagen types I and III, fibronectin, tenascin C, and matrix metalloproteinase 2 (MMP-2) were measured by real-time fluorescent quantitative PCR.

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  • Scaffold-Based Cartilage Treatments: With or Without Cells? A Systematic Review of Preclinical and Clinical Evidence

    Purpose

    Regenerative scaffold-based procedures are emerging as a potential therapeutic option for the treatment of chondral and osteochondral lesions. In general, we can summarize most of the recent developments to reach clinical application into 2 major trends: the use of different cell sources or the application of biomaterials as a cell-free approach. The aim of this systematic review was to analyze both preclinical and clinical studies on these new trends to understand how the available evidence supports the use of cell sources or justifies the cell-free approach for the scaffold-based treatment of cartilage lesions.

    Methods

    The research was performed using the PubMed database by looking at studies published in the English language referring to chondral or osteochondral defect repair with scaffold-based procedures until the end of 2013. The following strings were used: (\"cartilage\"[MeSH] AND \"tissue scaffolds\"[MeSH]).

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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.

    Read More

  • 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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