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  • Treatment of Articular Cartilage Injury Using Mesenchymal Stem Cells.

    Abstract

    Articular cartilage lesions can be a debilitating disease resulting in the development of osteoarthritis (OA). In recent years, mesenchymal stem cell (MSC) strategies combined with the microfracture technique are emerging as a powerful tool for cartilage repair. Even though there are some successful reports of MSCs treatments, many aspects have to be optimized such as best cell source and application method. The interest in this field is growing and randomized controlled trials are needed to show the potential of MSC treatment.

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  • Chondrogenically Primed Mesenchymal Stem Cell-Seeded Alginate Hydrogels Promote Early Bone Formation in Critically-Sized Defects

    Abstract

    Hypertrophic cartilaginous grafts can be engineered in vitro using bone marrow derived Mesenchymal Stem Cells (MSCs). When such engineered tissues are implanted in vivo they have been shown to induce bone formation by recapitulating aspects of the developmental process of endochondral ossification. Alginate, a naturally sourced and biocompatible hydrogel, offers an attractive 3D environment to facilitate the in vitro chondrogenesis of MSCs. Furthermore, such alginate hydrogels can potentially be used to engineer cartilage tissues of scale to promote endochondral bone regeneration in large bone defects. The aim of this study was to investigate the ability of chondrogenically-primed MSC-laden alginate hydrogels to induce healing in two distinct critically-sized defect models. Bone marrow derived MSCs were seeded into alginate hydrogels, chondrogenically primed in vitro in the presence of TGF-β3 and then implanted into either a critically-sized rat cranial or femoral defect. μCT analysis 4 weeks post-implantation revealed significantly higher levels of mineralization within the femoral defects treated with MSC-laden alginate hydrogels compared to untreated empty controls, with similar results observed within the cranial defects. However, any newly deposited bone was generated appositional to the alginate material, and occurred only superficially or where the alginate was seen to degrade. Alginate material was found to persist within both orthotopic locations 8 weeks post-implantation, with its slow rate of degradation appearing to prevent complete bone regeneration. In conclusion, while chondrogenically primed MSC-alginate constructs can act as templates to treat critically-sized defects within bones formed through either intramembranous or endochondral ossification, further optimization of the degradation kinetics of the hydrogel itself will be required to accelerate bone tissue deposition and facilitate complete regeneration of such defects.

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

    We would like to congratulate Barker et

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  • Treatment of Knee Osteoarthritis with Autologous Expanded Bone Marrow Mesenchymal Stem Cells: 50 Cases Clinical and MRI Results at One Year Follow-Up

    Abstract

    Knee osteoarthritis is one of the most prevalent joint diseases, causing pain, function loss and disability, leading to a progressive cartilage degeneration induced by biochemical changes in its composition. Current available treatments focus on addressing symptoms and joint replacement is the last treatment option.

    Advanced therapies with mesenchymal stem cells build new expectations to improve the results of OA treatments. MSC applied in animal models, show encouraging results in modulating inflammation and joint cartilage repair. Several studies applied autologous mesenchymal stem cells to treat knee osteoarthritis in humans by means of an intra-articular injection.

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  • A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain

    Abstract

    OBJECTIVES: Controversy exists regarding the efficacy of ligament prolotherapy in alleviating sacroiliac joint pain. The inconsistent success rates reported in previous studies may be attributed to variability in patient selection and techniques between studies. It was hypothesized that intra-articular prolotherapy for patients with a positive response to diagnostic block may mitigate the drawbacks of ligament prolotherapy. The purpose of this study was to evaluate the efficacy and long-term effectiveness of intra-articular prolotherapy in relieving sacroiliac joint pain, compared with intra-articular steroid injection.

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  • Therapeutic Potential of Differentiated Mesenchymal Stem Cells for Treatment of Osteoarthritis

    Abstract

    Osteoarthritis (OA) is a chronic, progressive, and irreversible degenerative joint disease. Conventional OA treatments often result in complications such as pain and limited activity. However, transplantation of mesenchymal stem cells (MSCs) has several beneficial effects such as paracrine effects, anti-inflammatory activity, and immunomodulatory capacity. In addition, MSCs can be differentiated into several cell types, including chondrocytes, OPEN ACCESS Int. J. Mol. Sci. 2015, 16 14962 osteocytes, endothelia, and adipocytes. Thus, transplantation of MSCs is a suggested therapeutic tool for treatment of OA. However, transplanted naׯve MSCs can cause problems such as heterogeneous populations including differentiated MSCs and undifferentiated cells. To overcome this problem, new strategies for inducing differentiation of MSCs are needed. One possibility is the application of microRNA (miRNA) and small molecules, which regulate multiple molecular pathways and cellular processes such as differentiation. Here, we provide insight into possible strategies for cartilage regeneration by transplantation of differentiated MSCs to treat OA patients.

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  • Stem Cell Therapies for Post-Traumatic Arthritis

    Post-traumatic arthritis (PTA) is a common condition that occurs in more than 40% of people who experience significant joint trauma, such as ligament injury, meniscal tear, or intra-articular fracture [1]. PTA is estimated to be responsible for 12% of all osteoarthritis (OA)

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  • Mesenchymal Stem Cell Implantation in Knee Osteoarthritis - An Assessment of the Factors Influencing Clinical Outcomes

    Abstract

    Background: Several clinical studies have reported on cell-based treatment using mesenchymal stem cells (MSCs) for cartilage regeneration in knee osteoarthritis (OA). However, little is known about the factors that influence the clinical outcomes after surgery.

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    Purpose/Hypothesis: This study aimed to investigate the clinical outcomes of MSC implantation in patients with knee OA and assess the factors that are associated with clinical outcomes. The hypothesis was that factors may exist that could influence clinical outcomes.

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  • Autologous Platelet-Rich Plasma Preparations - Influence of Nonsteroidal Anti-inflammatory Drugs on Platelet Function

    Abstract

    Background Autologous platelet-rich plasma (PRP) has been widely used for the treatment of sports injuries. It has been associated with improved healing and regeneration of soft tissues in elite athletes. Athletes are commonly receiving nonsteroidal anti-inflammatory drugs (NSAIDs). As yet, the effect of these drugs on platelet function in PRP formulations has not been taken into consideration.

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    Hypothesis The function of platelets in PRP produced under the influence of NSAIDs is inhibited and may lessen a possible healing effect on the site of injury.

    Study Design Controlled laboratory study.

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  • AB0853 €…Efficacy of Ultrasound-Guided Intra-Articular Injections of Platelet-Rich Plasma and Hyaluronic Acid for Hip Osteoarthritis

    Abstract

    Background The concentrated platelets found in Platelet Rich Plasma (PRP) include growth factors among the huge reservoirs of bioactive proteins that are vital to initiate and accelerate tissue repair and regeneration.

    Objectives To evaluate the assess the duration of effectiveness of 4 intra-articular injection: two infiltration of platelet gel followed by two ultrasound guided infiltration of hyaluronic acid under ultrasound (US) guidance in symptomatic osteoarthritis of the hip.

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  • Biomaterial Scaffolds for Mesenchymal Stem Cell Based Therapy Aimed at Tissue Engineering Application for Osteoarthritis

    Abstract

    RDegenerative joint diseases have seen a rise in the past few decades. Among them, the prevalence of Osteoarthritis (OA) is the highest as compared to the other types of arthritis. It involves the degradation of cartilage in joints that ultimately leads to their degeneration. Globally, it affects over 200 million people and the statistics are only expected to increase over the next few decades. The treatment approach for initial stages of OA involves changes in the lifestyle, use of analgesics, NSAIDs and other medications. As the condition worsens, the end point treatment is generally a prosthetic implant followed by surgery. These approaches are short-term and the patients are often found complaining of the post-surgical complications of the invasive methods. This has created the need for less invasive and sustainable treatment approaches. Mesenchymal stem cells (MSCs) have the potential to be differentiated into various kinds of cells making stem cell based therapy an attractive approach for both, researchers and medical experts. We aimed at fabricating biomaterials and microstructures that would provide these MSCs with support and would allow them to organize themselves. The biomaterial and micro-structures fabricated by the \"Layer-by-Layer\"(L-b-l) method exhibited extracellular matrix (ECM) like properties enhancing the adhesion and differentiation of the MSCs. Similar activity has been claimed by researchers of Osaka University who have filed a patent for self-organization for osteochondral regeneration. It was observed that the human MSCs organized themselves better on the biomaterial that we had fabricated for them. We also found that the micro-structures had the potential to give rise to a complex scaffold system.

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  • Regenerative Injection Treatment in the Spine: Review and Case Series with Platelet Rich Plasma

    Abstract

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    Background: Platelet-Rich Plasma (PRP) has been used for a variety of musculoskeletal disorders including tendinopathies and Osteoarthritis. Few\nstudies exist for PRP in the spine, except for studies involving disc pathology. However, numerous studies exist involving the use of Prolotherapy for spinal disorders. Both Prolotherapy and PRP can be considered within the broad category of Regenerative Injection Treatment (RIT), which are proposed to strengthen or repair injured ligaments, tendons, muscle, cartilage, and bone via injections of proliferative solutions, growth factors, or cells. Provided that double blind randomized controlled trials have shownboth PRP and Prolotherapy to be effective in treating similar regions of the body, it is reasonable to consider that PRP could be comparatively effective as Prolotherapy in treating pain related to the facet joints, capsules and associated spinal ligaments.

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  • Platelet-Rich Plasma Promotes Axon Regeneration, Wound Healing, and Pain Reduction: Fact or Fiction

    Abstract

    Platelet-rich plasma (PRP) has been tested in vitro, in animal models, and clinically for its efficacy in enhancing the rate of wound healing, reducing pain associated with injuries, and promoting axon regeneration. Although extensive data indicate that PRP-released factors induce these effects, the claims are often weakened because many studies were not rigorous or controlled, the data were limited, and other studies yielded contrary results. Critical to assessing whether PRP is effective are the large number of variables in these studies, including the method of PRP preparation, which influences the composition of PRP; type of application; type of wounds; target tissues; and diverse animal models and clinical studies. All these variables raise the question of whether one can anticipate consistent influences and raise the possibility that most of the results are correct under the circumstances where PRP was tested. This review examines evidence on the potential influences of PRP and whether PRP-released factors could induce the reported influences and concludes that the preponderance of evidence suggests that PRP has the capacity to induce all the claimed influences, although this position cannot be definitively argued. Well-defined and rigorously controlled studies of the potential influences of PRP are required in which PRP is isolated and applied using consistent techniques, protocols, and models. Finally, it is concluded that, because of the purported benefits of PRP administration and the lack of adverse events, further animal and clinical studies should be performed to explore the potential influences of PRP.

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  • Does Intra-articular Platelet-Rich Plasma Injection Provide Clinically Superior Outcomes Compared With Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review of Overlapping Meta-analyses

    Purpose

    The aims of this study were (1) to perform a systematic review of meta-analyses evaluating platelet-rich plasma (PRP) injection in the treatment of knee joint cartilage degenerative pathology, (2) to provide a framework for analysis and interpretation of the best available evidence to provide recommendations for use (or lack thereof) of PRP in the setting of knee osteoarthritis (OA), and (3) to identify literature gaps where continued investigation would be suggested.

    Methods

    Literature searches were performed for meta-analyses examining use of PRP versus corticosteroids, hyaluronic acid, oral nonsteroidal anti-inflammatory drugs, or placebo. Clinical data were extracted, and meta-analysis quality was assessed. The Jadad algorithm was applied to determine meta-analyses that provided the highest level of evidence.

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  • Yes-associated protein (YAP) is a negative regulator of chondrogenesis in mesenchymal stem cells

    Introduction

    The control of differentiation of mesenchymal stromal/stem cells (MSCs) is crucial for tissue engineering strategies employing MSCs. The purpose of this study was to investigate whether the transcriptional co-factor Yes-associated protein (YAP) regulates chondrogenic differentiation of MSCs.

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    Methods

    Expression of total YAP, its paralogue transcriptional co-activator with PDZ-binding motif (TAZ), and individual YAP transcript variants during in vitro chondrogenesis of human MSCs was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). YAP expression was confirmed by western blotting. To determine the effect of high YAP activity on chondrogenesis, C3H10T1/2 MSC-like cells were transduced with human (h)YAP and treated in micromass with bone morphogenetic protein-2 (BMP-2). Chondrogenic differentiation was assessed by alcian blue staining and expression of chondrocyte-lineage genes. BMP signalling was determined by detection of pSmad1,5,8 by western blotting and expression of BMP target genes by quantitative RT-PCR. Finally, YAP and pYAP were detected in mouse embryo hindlimbs by immunohistochemistry.

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  • Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model € 

    Abstract

    This study was carried out to assess the feasibility of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in articular cartilage repair and to further determine a suitable delivering hydrogel in a rat model. Critical sized full thickness cartilage defects were created. The hUCB-MSCs and three different hydrogel composites (hydrogel A; 4% hyaluronic acid/30% pluronic (1:1, v/v), hydrogel B; 4% hyaluronic acid, and hydrogel C; 4% hyaluronic acid/30% pluronic/chitosan (1:1:2, v/v)) were implanted into the experimental knee (right knee) and hydrogels without hUCB-MSCs were implanted into the control knee (left knee). Defects were evaluated after 8 weeks. The hUCB-MSCs with hydrogels composites resulted in a better repair as seen by gross and histological evaluation compared with hydrogels without hUCB-MSCs. Among the three different hydrogels, the 4% hyaluronic acid hydrogel composite (hydorgel B) showed the best result in cartilage repair as seen by the histological evaluation compared with the other hydrogel composites (hydrogel A and C). The results of this study suggest that hUCB-MSCs may be a promising cell source in combination with 4% hyaluronic acid hydrogels in the in vivo repair of cartilage defects. This article is protected by copyright. All rights reserved

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  • Platelet-rich plasma increases proliferation of tendon cells by modulating Stat3 and p27 to up-regulate expression of cyclins and cyclin-dependent kinases

    Objectives

    To investigate effects of platelet-rich plasma on tendon cell proliferation and the underlying molecular mechanisms.

    Materials and methods

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    Platelet-rich plasma was prepared manually by two-step centrifugation. Proliferation was evaluated in cultured rat tendon cells by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Cell cycle progression was assessed by flow cytometry. Messenger RNA expression of proliferating cell nuclear antigen (PCNA), cyclin E1, A2 and B1, and cyclin-dependent kinases (Cdks) 1 and 2 was assessed by real-time polymerase chain reaction. Protein expression of the above cyclins and Cdks and of signal transducer and activator of transcription (Stat) 3 and p27 was evaluated by western blotting.

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  • Human somatic stem cell-based therapy for cartilage regeneration

    Abstract

    Clinical investigations using human somatic tissue derived stem cells for a variety of different diseases have been performed. Neural crest-derived stem cells exhibit somatic organization, can contribute to mesenchymal stem/stromal cells (MSCs) (1) and are used for cartilage treatment, bone reconstruction and anti-inflammatory treatments for diseases. The most common cell source for cartilage treatment is MSCs (2,3). Many clinical studies have used neural crest-derived stem cells (or MSCs) from different tissues and different methodologies. These differences in the generation of somatic tissue-derived stem cells have led to variable results in clinical studies. Although stem cell properties have been poorly characterized, human trials are presently under way.

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  • Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients

    Abstract

    Aim : Osteoarthritis is a degenerative joint disease characterized by the destruction of joint cartilage. Mesenchymal stem cells (MSCs) are found in low numbers in normal cartilage, mainly in the superficial layer, acting as repairing agents. In OA, MSCs are seen in larger numbers, but act chaotic and are unable to repair the cartilage. The synovial membrane becomes inflamed and interacts with the cartilage. Transplanted MSC have the ability to normalize them, redirecting them to their normal function. In a preliminary study, we showed that MSC could improve knee OA in four patients at 6

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  • Strategies to stimulate mobilization and homing of endogenous stem and progenitor cells for bone tissue repair

    Abstract

    The gold standard for the treatment of critical sized bone defects is autologous or allogenic bone graft. This has several limitations including donor site morbidity and the restricted supply of graft material. Cell-based tissue engineering strategies represent an alternative approach. Mesenchymal stem cells (MSCs) have been considered as a source of osteoprogenitor cells. More recently, focus has been placed on the use of endothelial progenitor cells (EPCs), since vascularization is a critical step in bone healing. Although many of these approaches have demonstrated effectiveness for bone regeneration, cell-based therapies require time consuming and cost expensive in vitro cell expansion procedures. Accordingly, research is becoming increasingly focused on the homing and stimulation of native cells. The stromal cell-derived factor 1 (SDF-1) - CXCR4 axis has been shown to be critical for the recruitment of MSCs and EPCs. Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and has been targeted in many studies. Here, we present an overview of the different approaches for delivering homing factors to the defect site by absorption or incorporation to biomaterials, gene therapy or via genetically manipulated cells. We further review strategies focusing on the stimulation of endogenous cells to support bone repair. Finally, we discuss the major challenges in the treatment of critical size bone defects and fracture non-unions.

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