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  • The Addition of Platelet-Rich Plasma to Scaffolds Used for Cartilage Repair: A Review of Human and Animal Studies

    Purpose

    To review the available literature on studies focusing on platelet-rich plasma (PRP)-enhanced scaffolds for cartilage lesion repair in animals and to analyze the clinical outcomes of similar biologically augmented cartilage regeneration techniques in humans.

    Methods

    We conducted a literature search and subsequent review investigating the potential of PRP to enhance articular cartilage repair using scaffolds or bioengineered implants.

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  • Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial

    Abstract

    Background: Osteoarthritis is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. Conventional treatments demonstrate only modest clinical benefits without lesion reversal. Autologous mesenchymal stromal cell (MSC) treatments have shown feasibility, safety, and strong indications for clinical efficacy. We performed a randomized, active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs, and we obtain information regarding the efficacy of this treatment.

    Methods: We randomized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients. The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 x 106 cells. The control group received intra-articular hyaluronic acid (60 mg, single dose). Clinical outcomes were followed for 1 year and included evaluations of pain, disability, and quality of life. Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping.

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  • Stimulation of the Superficial Zone Protein and Lubrication in the Articular Cartilage by Human Platelet-Rich Plasma

    Abstract

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    Background: Platelet-rich plasma (PRP) contains high concentrations of autologous growth factors that originate from platelets. Intra-articular injections of PRP have the potential to ameliorate the symptoms of osteoarthritis in the knee. Superficial zone protein (SZP) is a boundary lubricant in articular cartilage and plays an important role in reducing friction and wear and therefore is critical in cartilage homeostasis.

    Purpose: To determine if PRP influences the production of SZP from human joint-derived cells and to evaluate the lubricating properties of PRP on normal bovine articular cartilage.

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  • Platelet-rich plasma injection as an effective treatment for temporomandibular joint osteoarthritis

    Abstract

    Purpose

    Emerging evidence suggests that platelet-rich plasma (PRP) might be of assistance in the treatment of degenerative conditions of the joints. The aim of this study was to compare the uses of PRP and the hyaluronic acid (HA) in treatment of temporomandibular joint (TMJ) osteoarthritis with a long-term follow-up.

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  • Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention

    Abstract

    Osteoarthritis (OA) is associated with articular cartilage abnormalities and affects people of older age: preventative or therapeutic treatment measures for OA and related articular cartilage disorders remain challenging. In this perspective review, we have integrated multiple biological, morphological, developmental, stem cell and homeostasis concepts of articular cartilage to develop a paradigm for cartilage regeneration. OA is conceptually defined as an injury of cartilage that initiates chondrocyte activation, expression of proteases and growth factor release from the matrix. This regenerative process results in the local activation of inflammatory response genes in cartilage without migration of inflammatory cells or angiogenesis. The end results are catabolic and anabolic responses, and it is the balance between these two outcomes that controls remodelling of the matrix and regeneration. A tantalizing clinical clue for cartilage regrowth in OA joints has been observed in surgically created joint distraction. We hypothesize that cartilage growth in these distracted joints may have a biological connection with the size of organs and regeneration. Therefore we propose a novel, practical and nonsurgical intervention to validate the role of distraction in cartilage regeneration in OA. The approach permits normal wake-up activity while during sleep; the index knee is subjected to distraction with a pull traction device. Comparison of follow-up magnetic resonance imaging (MRI) at 3 and 6 months of therapy to those taken before therapy will provide much-needed objective evidence for the use of this mode of therapy for OA. We suggest that the paradigm presented here merits investigation for treatment of OA in knee joints.

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  • Percutaneous injection of bone marrow mesenchymal stem cells for ankle non-unions decreases complications in patients with diabetes

    Abstract

    Purpose : Clinical studies in diabetic patients have demonstrated that there is a high incidence of complications in distal tibia and ankle fracture treatments. One strategy to mitigate issues with wound healing and infection in diabetic patients is to use a percutaneous technique in which autologous, bone marrow-derived, concentrated cells are injected at the site of non-unions

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  • Meeting current musculoskeletal health demand through deeper insights into tissue homeostasis and regeneration

    The burden of chronic musculoskeletal disorders is challenging and prompts therapeutic advancements. The notion that chronic conditions such as osteoarthritis and tendinopathy are linked to deficient healing by failure of one or several of the cellular/molecular processes involved is gaining ground. Alterations underpinning disruption of healing mechanisms that contribute to the development of chronic musculoskeletal pathologies include unresolved inflammation, abnormal angiogenic status, alterations in paracrine communication, decline in stem cell functioning and inability to maintain homeostasis in the extracellular matrix compartment. The complexity of failed healing may be challenged with interventions that target multiple biological processes such as cell therapies and/or platelet-rich plasma.

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  • A new in vivo stem cell model for regenerative rheumatology

    With advances in stem cell techniques for the bioengineering and regeneration of musculoskeletal tissues comes added complexity in our understanding of stem cell biology. How will the recent discovery of a novel stem cell subset, termed osteochondroreticular stem cells, contribute to progression in the field?

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  • Harnessing stem cell potential for regenerative medicine and cell-based therapy

    Abstract

    Stem cells have an interesting history, hugely replete with varied discourse, debate and controversy. Researchers, in mid 1800s, discovered that cells were basically the building blocks of life, and that some cells had the ability to produce other cells. Later on, owing to several years of relentless thinking and efforts, mammalian eggs could be fertilised outside of the human body. In the early 1900s, cells with remarkable ability to generate blood cells were identified. After a gap of 8-9 decades, researchers discovered blood producing stem cells, called as hematopoietic stem cells, followed by another resident of bone marrow stem cells, named as mesenchymal stem cells. Furthermore, during the first decade of 21st century, scientists successfully programmed differentiated somatic cells into stem cell-like cell that was called as induced pluripotent stem cells (iPSCs). The greatest advantages of the iPSCs, apart from being a potential prospective candidate for cell therapy, is the lack of any ethical concerns like other category of stem cells, such as embryonic stem cells (ESCs). Besides, stem cells are also being used to generate multiple functional organs in vitro to study, and explicitly decipher the structural organisation and concerted working of these vital organs in the human body, which will further help in deepening the insight, understanding and designing new therapeutic strategy to ameliorate and cure the multiple diseases. Recent findings have proved that the stem cells may offer shining rays of hope, and be explored for treatment of deadly degenerative and incurable diseases in years to come.

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  • Simulation and Hardware Implementetation of Grid Connected Solar Charge Controller with MPPT

    Abstract

    A renewable energy source plays an important role in electricity generation. Various renewable energy sources like wind, solar, geothermal, ocean thermal, and biomass can be used for generation of electricity and for meeting our daily energy needs. Energy from the sun is the best option for electricity\ngeneration as it is available everywhere and is free to harness. On an average the sunshine hour in India is about 6hrs annually also the sun shine shines in India for about 9 months in a year. Electricity from the sun can be generated through the solar photovoltaic modules (SPV). The SPV comes in various power output to meet the load requirement [1]. Maximization of power from a solar photo voltaic module (SPV) is of special interest as the efficiency of the SPV module is very low. A peak power tracker and DC-DC Boost Converter is used for Extracting the maximum power from the SPV module. And simulation in PSIM software and hardware result is compare and solar panel maximum efficiencies is increase nearby 85% using dither routine algorithm method use.

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  • Fluocinolone Acetonide is a Potent Synergistic Factor of TGF-β3-Associated Chondrogenesis of Bone Marrow-Derived Mesenchymal Stem Cells for Articular Surface Regeneration € 

    Abstract

    Articular cartilage repair remains a challenging problem. Based on a high-throughput screening and functional analysis, we found that fluocinolone acetonide (FA) in combination with transforming growth factor beta 3 (TGF-β3) strongly potentiated chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). In an in vivo cartilage defect model in knee joints of immunocompromised mice, transplantation of FA/TGF-β3-treated hBMSCs could completely repair the articular surface. Analysis of the intracellular pathways revealed that FA enhanced TGF-β3-induced phosphorylation of Smad2 and Smad3. Additionally, we performed a pathway array and found that FA activates mTORC1/AKT pathway. Chemical inhibition of mTORC1 with rapamycin substantially suppressed FA effect, and inhibition of AKT completely repressed chondrogenesis of hBMSCs. Inhibition of glucocorticoid receptor with mifepristone also suppressed FA effect, suggesting that FA involves binding to glucocorticoid receptor. Comparative analysis with other glucocorticoids (triamcinolone acetonide (TA) and dexamethasone (DEX)) revealed the unique ability of FA to repair articular cartilage surgical defects. Analysis of intracellular pathways showed that mTORC1/AKT pathway and glucocorticoid receptor was highly activated with FA and TA, but to a less extent with DEX. Collectively, these results show a unique ability of FA to enhance TGF-β3-associated chondrogenesis, and suggest that the FA/TGF-β3 combination may be used as major inducer of chondrogenesis in vitro. Additionally, FA/TGF-β3 could be potentially applied in a clinical setting to increase the efficiency of regenerative approaches based on chondrogenic differentiation of stem cells. This article is protected by copyright. All rights reserved.

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  • Musculoskeletal biology and bioengineering: A new in vivo stem cell model for regenerative rheumatology

    With advances in stem cell techniques for the bioengineering and regeneration of musculoskeletal tissues comes added complexity in our understanding of stem cell biology. How will the recent discovery of a novel stem cell subset, termed osteochondroreticular stem cells, contribute to progression in the field?

    Read more

  • Future of Cell-Based Therapies in Orthopedic Sports Medicine

    Abstract

    Orthopedic Sports Medicine involves the treatment of complex injuries in both the acute and chronic setting. Massive tears of soft tissue, large hard tissue breaks, or malalignments or catastrophic collapse of both soft and hard tissue structures require clever surgical intervention both as open or arthroscopic procedures. Small tears or fractures or resistant chronic, nonhealing, and often painful conditions are a challenge to the orthopedic practitioner. My prediction for the future is that cell-based therapies will provide the key to these clinically challenging situations. Specifically, the use of either autologous or allogeneic mesenchymal stem cells (MSCs) can and will provide clinical solutions (Caplan 2009; Caplan and Correa 2011).

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  • Hydrostatic pressure promotes the proliferation and osteogenic/chondrogenic differentiation of mesenchymal stem cells: the roles of RhoA and Rac1

    Abstract

    Our previous studies have shown that hydrostatic pressure can serve as an active regulator for bone marrow mesenchymal stem cells (BMSCs). The current work further investigates the roles of cytoskeletal regulatory proteins Ras homolog gene family member A (RhoA) and Ras-related C3 botulinum toxin substrate 1 (Rac1) in hydrostatic pressure-related effects on BMSCs. Flow cytometry assays showed that the hydrostatic pressure promoted cell cycle initiation in a RhoA- and Rac1-dependent manner. Furthermore, fluorescence assays confirmed that RhoA played a positive and Rac1 displayed a negative role in the hydrostatic pressure-induced F-actin stress fiber assembly. Western blots suggested that RhoA and Rac1 play central roles in the pressure-inhibited ERK phosphorylation, and Rac1 but not RhoA was involved in the pressure-promoted JNK phosphorylation. Finally, real-time polymerase chain reaction (PCR) experiments showed that pressure promoted the expression of osteogenic marker genes in BMSCs at an early stage of osteogenic differentiation through the up-regulation of RhoA activity. Additionally, the PCR results showed that pressure enhanced the expression of chondrogenic marker genes in BMSCs during chondrogenic differentiation via the up-regulation of Rac1 activity. Collectively, our results suggested that RhoA and Rac1 are critical to the pressure-induced proliferation and differentiation, the stress fiber assembly, and MAPK activation in BMSCs.

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  • The Role of Stem Cells and Tissue Engineering in Orthopaedic Sports Medicine: Current Evidence and Future Directions

    Abstract

    The use of stem cell therapies for the treatment of orthopaedic injuries continues to advance. The purpose of this review was to provide an update of the current role and future directions of stem cell strategies in sports medicine. The application of cell-based treatments in the sports medicine arena has expanded in recent years. Promising preclinical results have led to translation of these novel therapies into the clinical setting. Early well-designed comparative clinical studies have also shown positive outcomes. Despite significant advances in this arena, there remains a need for additional high-powered and well-designed clinical trials to confirm the safety and efficacy of treatment.

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  • Mesenchymal Stem Cell Implantation in Osteoarthritic Knees Is Fibrin Glue Effective as a Scaffold?

    Abstract

    Background: The cell-based tissue engineering approach that uses mesenchymal stem cells (MSCs) has addressed the issue of articular cartilage repair in osteoarthritic (OA) knees. However, to improve outcomes, an advanced surgical procedure with tissue-engineered scaffolds may be needed to treat patients with large cartilage lesions.

    Purpose: To investigate the clinical and second-look arthroscopic outcomes of the implantation of MSCs loaded in fibrin glue as a scaffold in patients with OA knees and to compare these outcomes with those of MSC implantation without a scaffold.

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  • TGF-b1, GDF-5, and BMP-2 Stimulation Induces Chondrogenesis in Expanded Human Articular Chondrocytes and Marrow-Derived Stromal Cells

    Abstract

    Replacement of degenerated cartilage with cell-based cartilage products may offer a long-term solution to halt arthritis'   degenerative   progression. Chondrocytes   are   frequently   used   in   cell- based   FDA-approved   cartilage   products;   yet   human   marrow-derived   stromal   cells   (hMSCs)   show signicant   translational   potential, reducing   donor   site   morbidity   and   maintaining   their   undiffer- entiated   phenotype   with   expansion.   This   study   sought   to   investigate   the   effects   of   transforming growth   factor     b1   (TGF-b1),   growth/differentiation   factor   5   (GDF-5),   and   bone   morphogenetic protein   2   (BMP-2)   during   postexpansion   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   broblastic   genes.   However,   following   expansion,   10   ng/mL   TGF-b1,   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-b1,   GDF-5,   and   BMP-2   induced the   greatest   upregulation   of   chondrogenic   genes,   that   is,   Col2A1,   Col2A1/Col1A1   ratio,   SOX9, and   ACAN,   and   synthesis   of   cartilage-specic   matrix,   that   is,   glycosaminoglycans   (GAGs)   and ratio   of   collagen   II/I.   Finally,   TGF-b1,   GDF-5,   and   BMP-2   stimulation   yielded   mechanically   robust cartilage   rich   in   collagen   II   and   GAGs   in   both   cell   types,   following   4   weeks   maturation.   This study   illustrates   notable   success   in   using   the   self-assembling   method   to   generate   robust, scaffold-free   neocartilage   constructs   using   expanded   hACs   and   hMSCs. STEM     CELLS 2015;33:762-773

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  • Advanced cell therapies for articular cartilage regeneration

    Advanced cell-based therapies are promising approaches for stimulating full regeneration of cartilage lesions. In addition to a few commercially available medicinal pro-ducts, several clinical and preclinical studies are ongoing worldwide. In preclinical settings, high-quality cartilage tissue has been produced using combination strategies involving stem or progenitor cells, biomaterials, and bio-molecules to generate a construct for implantation at the lesion site. Cell numbers and mechanical stimulation of the constructs are not commonly considered, but are important parameters to be evaluated in forthcoming clinical studies. We review current clinical and preclinical studies for advanced therapy cartilage regeneration and evaluate the progress of the field.

    Advanced cell-based therapies are promising approaches for stimulating full regeneration of cartilage lesions. In addition to a few commercially available medicinal products, several clinical and preclinical studies are ongoing worldwide. In preclinical settings, high-quality cartilage tissue has been produced using combination strategies involving stem or progenitor cells, biomaterials, and bio-molecules to generate a construct for implantation at the lesion site. Cell numbers and mechanical stimulation of the constructs are not commonly considered, but are important parameters to be evaluated in forthcoming clinical studies. We review current clinical and preclinical studies for advanced therapy cartilage regeneration and evaluate the progress of the field.

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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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