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  • Translation of cell therapy into clinical practice: validation of an application procedure for bone marrow progenitor cells and platelet rich plasma.

    Abstract

    Tissue regeneration can be improved by local application of autologous bone marrow derived progenitor cells (BMSC) and platelet rich plasma (PRP). However, there is a lack of standardized application procedures for clinical use. Therefore, a technique in accordance with the guidelines for advanced therapies medical products of the European Medicine Agency was developed and established.In detail, a process for the isolation and formulation of autologous bone marrow cells (BMC) and PRP in a clinical setting was validated. To investigate the influence of storage time and temperature on gel formation and gel stability, different concentrations of BMC were stored with and without additional platelets, thrombin and fibrinogen and analyzed over a period of 28 days. In addition, cell vitality using a live-dead staining and migration ability of human mesenchymal stem cells (hMSC) in the gel clot was investigated.For an optimized stable gel clot, human BMC and PRP should be combined with 10% to 20% fibrinogen (9 mg/mL to 18 mg/mL) and 5% to 20% thrombin (25 I.E. to 100 I.E.). Both freshly prepared and stored cells for 1 to 7 days had a stable consistence over 28 days at 37

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  • Effect of bone marrow-derived stem cells on chondrocytes from patients with osteoarthritis

    Abstract

    Increasing numbers of individuals are suffering from osteoarthritis every year, and the directed intra-articular injection of bone marrow stem cells has provided a promising treatment strategy for osteoarthritis. Although a number of studies have demonstrated that intra-articular injection of bone marrow stem cells produced desirable results, the mechanism underlying this effect has not been elucidated. In the current study, the effect of bone marrow stem cells on chondrocytes from patients with osteoarthritis was observed in a co-culture system. Human chondrocytes were obtained from patients with osteoarthritis who underwent surgical procedures and bone marrow stem cells were obtained from bone marrow aspirates, and then the chondrocytes were then cultured alone or cocultured with bone marrow stem cells in 0.4-

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  • Real-time-guided bone regeneration around standardized critical size calvarial defects using bone marrow-derived mesenchymal stem cells and collagen membrane with and without using tricalcium phosphate: an in vivo micro-computed tomographic and histologic

    Abstract

    The aim of the present real time in vivo micro-computed tomography (µCT) and histologic experiment was to assess the efficacy of guided bone regeneration (GBR) around standardized calvarial critical size defects (CSD) using bone marrow-derived mesenchymal stem cells (BMSCs), and collagen membrane (CM) with and without tricalcium phosphate (TCP) graft material. In the calvaria of nine female Sprague-Dawley rats, full-thickness CSD (diameter 4.6 mm) were created under general anesthesia. Treatment-wise, rats were divided into three groups. In group 1, CSD was covered with a resorbable CM; in group 2, BMSCs were filled in CSD and covered with CM; and in group 3, TCP soaked in BMSCs was placed in CSD and covered with CM. All defects were closed using resorbable sutures. Bone volume and bone mineral density of newly formed bone (NFB) and remaining TCP particles and rate of new bone formation was determined at baseline, 2, 4, 6, and 10 weeks using in vivo µCT. At the 10th week, the rats were killed and calvarial segments were assessed histologically. The results showed that the hardness of NFB was similar to that of the native bone in groups 1 and 2 as compared to the NFB in group 3. Likewise, values for the modulus of elasticity were also significantly higher in group 3 compared to groups 1 and 2. This suggests that TCP when used in combination with BMSCs and without CM was unable to form bone of significant strength that could possibly provide mechanical “lock” between the natural bone and NFB. The use of BMSCs as adjuncts to conventional GBR initiated new bone formation as early as 2 weeks of treatment compared to when GBR is attempted without adjunct BMSC therapy.

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  • The effect of sub-epineural platelet-rich plasma (PRP) on regeneration of the sciatic nerve in a rat model

    Abstract:

    Background: Peripheral nerve injury is one of the most challenging of modern surgical problem. Recent advances in understanding the physiological and molecular pathways demonstrated the important role of growth factors in peripheral nerve regeneration. Platelet-rich plasma (PRP) is a biological product that has many growth factors. The aim of this study was to investigate the effect of PRP in the regeneration of sciatic nerve crush in the rat model.Methods: In this experimental study that established in the animal lab of the Hazrat Fatemeh Hospital in Tehran from September to October 2013, Twenty-four healthy male Sprague-Dawley rats (200-250 g) were randomly divided into two groups. In all rats the sciatic nerve was cut and then carefully repaired by the tension free method under a light microscope. In group 1, after the repair, 0.05

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  • Short term results comparison of intraarticular platelet-rich plasma (prp) and hyaluronic acid (ha) applications in early stage of knee osteoarthritis

    Abstract

    Objective:

    The aim of this study is to compare the short-term results of intra-articular platelet-rich plasma (PRP) and hyaluronic acid (HA) administrations in early knee osteoarthritis. Materials and methods: One hundred and eighteen patients (mean age: 59.3

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  • Bone Marrow Stem Cells in Response to Intervertebral Disc-Like Matrix Acidity and Oxygen Concentration - Implications for Cell-Based Regenerative Therapy

    Abstract

    Study Design. In vitro culture of porcine bone marrow stem cells (BMSCs) in varying pH microenvironments in a 3D hydrogel system.

    Objective. To characterise the response of BMSCs to varying pH environments (blood (pH 7.4), healthy IVD (pH 7.1), mildly degenerated IVD (pH 6.8) and severely degenerated IVD (pH 6.5) in 3D culture under normoxic (20%) and hypoxic (5%) conditions.

    Summary of Background Data. The intervertebral disc (IVD) is an avascular organ relying on diffusion of essential nutrients through the cartilaginous endplates (CEPs) thereby creating a challenging microenvironment. Within a degenerated IVD, oxygen and glucose concentrations decrease further (<5% oxygen, <5 mM glucose) and matrix acidity (

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  • Single injection of platelet-rich plasma as a novel treatment of carpal tunnel syndrome

    Abstract

    Both in vitro and in vivo experiments have confirmed that platelet-rich plasma has therapeutic effects on many neuropathies, but its effects on carpal tunnel syndrome remain poorly understood. We aimed to investigate whether single injection of platelet-rich plasma can improve the clinical symptoms of carpal tunnel syndrome. Fourteen patients presenting with median nerve injury who had suffered from mild carpal tunnel syndrome for over 3 months were included in this study. Under ultrasound guidance, 1-2 mL of platelet-rich plasma was injected into the region around the median nerve at the proximal edge of the carpal tunnel. At 1 month after single injection of platelet-rich plasma, Visual Analogue Scale results showed that pain almost disappeared in eight patients and it was obviously alleviated in three patients. Simultaneously, the disabilities of the arm, shoulder and hand questionnaire showed that upper limb function was obviously improved. In addition, no ultrasonographic manifestation of the carpal tunnel syndrome was found in five patients during ultrasonographic measurement of the width of the median nerve. During 3-month follow-up, the pain was not greatly alleviated in three patients. These findings show very encouraging mid-term outcomes regarding use of platelet-rich plasma for the treatment of carpal tunnel syndrome.

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  • The effect of platelet-rich plasma injection on lateral epicondylitis following failed conservative management

    Abstract

    Objective

    We assessed the effect PRP injection on pain and function in patients with lateral epicondylitis where conservative management had failed.

    Methods

    We prospectively reviewed 34 patients. The mean follow-up was 26 weeks (range 6-114 weeks). We used the Oxford Elbow Score (OES) and progression to surgery to assess outcomes.

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  • Effect of Dynamic Culture and Periodic Compression on Human Mesenchymal Stem Cell Proliferation and Chondrogenesis

    Abstract

    We have recently developed a bioreactor that can apply both shear and compressive forces to engineered tissues in dynamic culture. In our system, alginate hydrogel beads with encapsulated human mesenchymal stem cells (hMSCs) were cultured under different dynamic conditions while subjected to periodic, compressive force. A customized pressure sensor was developed to track the pressure fluctuations when shear forces and compressive forces were applied.

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  • Intra-Articular Injection of Synovium-Derived Mesenchymal Stem Cells with Hyaluronic Acid Can Repair Articular Cartilage Defects in a Can ine Model

    Abstract

    Objective:

    The purpose of this study was to evaluate effectiveness of intra-articular injection of synovium-derived mesenchymal stem cells (SMSCs) and hyaluronic acid (HA) for the treatment of articular cartilage defects in a canine model.

    Methods:

    Forty-eight knees of 24 beagle dogs were randomly assigned to 16 groups (n=3) according to both the number of injected SMSCs (0.5×—105cells, 5×—106cells, 5×—107cells) and the concentration of HA (0%, 0.01%, 0.1%, 0.5%). A partial-thickness cartilage defect was created in the medial femoral condyle under arthroscopy. After seven weeks, autologous SMSCs with or without 1 ml HA were percutaneously injected into the injured knee. In the control group, 1 ml saline was injected. Twelve weeks after the injection, evaluation was performed using the International Cartilage Repair Society (ICRS) visual assessment scale and the modified O\'Driscoll histological score.

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  • Stem Cell Therapies in Orthopaedic Trauma

    Marcucio, Ralph S. PhD; Nauth, Aaron MD; Giannoudis, Peter V. MD, FRCS; Bahney, Chelsea PhD; Piuzzi, Nicolas S. MD; Muschler, George MD; Miclau, Theodore III MD\nJournal of Orthopaedic Trauma December 2015 Vol. 29 - Issue : p S24-S27

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  • Using mesenchymal stem cells as a therapy for bone regeneration and repairing

    Abstract

    Bone is a unique tissue which could regenerate completely after injury rather than heal itself with a scar. Compared with other tissues the difference is that, during bone repairing and regeneration, after the inflammatory phase the mesenchymal stem cells (MSCs) are recruited to the injury site and differentiate into either chondroblasts or osteoblasts precursors, leading to bone repairing and regeneration. Besides these two precursors, the MSCs can also differentiate into adipocyte precursors, skeletal muscle precursors and some other mesodermal cells. With this multilineage potentiality, the MSCs are probably used to cure bone injury and other woundings in the near future. Here we will introduce the recent developments in understanding the mechanism of MSCs action in bone regeneration and repairing.

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  • Endoscopic plantar fasciotomy versus injection of platelet-rich plasma for resistant plantar fasciopathy

    Abstract

    Background

    Resistant plantar fasciopathy is a common orthopedic problem.

    Aim

    Comparing two different methods of treatment.

    Methods

    Fifty patients with chronic resistant plantar fasciopathy were divided into two groups. The first included 23 patients treated by endoscopic release of plantar fascia (EPF) and the second included 27 patients treated by injection of platelet-rich plasma (PRP).

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  • A study of autologous stem cells therapy assisted regeneration of cartilage in avascular bone necrosis

    Abstract

    Application of \'regenerative medicine\' has given a new hope to surgeons for the treatment of several chronic diseases and disorders including severe orthopedic conditions. There are a myriad of orthopedic conditions and injuries that presently have limited therapeutic treatments and could benefit from new developing therapies in regenerative medicine with the help of stem cell therapy1. Regenerative medicine therapies are mainly based on the applications of stem cells. Stem cells play a vital role in orthopedic treatments and the studies have shown to have promising results in repair of bone, tendon, cartilage including avascular necrosis (AVN), spondylitis etc. Bone and cartilage regeneration ability of stem cells has been demonstrated clinically. However, success rate may not be same in every case and it depends on the patient profile. Several factors can be responsible for the same which include patient\'s immune response, the type and grade of the disease, which along with other confounding factors decide the outcome of the treatment. In this paper we have presented some of the orthopedic case studies performed through autologous transplantation of the stem cells.

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  • Platelet-Rich Plasma in Muscle Injuries: When and How It Can Be Used

    Abstract

    Presenting a significant problem in clinical medicine, skeletal muscle regeneration (after injuries, in atrophic disorders, etc.) is limited by fibrous scar formation, slow healing time, and a high rate of injury recurrence. Unfortunately, not many alternatives exist to the generally accepted conservative RICE principle for treating muscle injuries. Local platelet-rich plasma (PRP) application is popular in the field of sports medicine as an autologous source of growth factors that are believed to have potential therapeutic implications. However, several concerns have been raised as to whether high concentrations of TGF-β contained in PRP itself may have a negative effect in regard to fibrosis and the lack of any preclinical data. Although it is believed to be already used by many sports physicians, there is no evidence-based protocol for using PRP in treating muscle injuries. This chapter explains the reason behind it and proposes the best time frame to use PRP in muscle injuries according to physiological healing processes.

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  • The Effects of Prolotherapy With Hypertonic Dextrose Versus Prolozone (Intraarticular Ozone) in Patients With Knee Osteoarthritis

    Abstract

    Background: Knee osteoarthritis (KOA) is a common disabling disease. Limited studies have demonstrated that prolotherapy with dextrose or with prolozone can be helpful in the treatment of patients with KOA.

    Objectives: In the current study, we compared the results between these two treatment methods.

    Patients and Methods: In the current randomized clinical trial, 80 patients with mild to moderate KOA were randomly assigned equally into two groups (ozone group and dextrose group). In each group, injections were repeated three times with 10-day intervals. Before the treatment and 3 months after the injections, the pain intensity was measured by using a visual analogue scale and the Western Ontario and McMaster university arthritis index scores. Finally, the results were compared between the two groups.

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  • Comparison of the Cellular Composition and Cytokine-Release Kinetics of Various Platelet-Rich Plasma Preparations

    Abstract

    Background: Variations in formulations used to prepare platelet-rich plasmas (PRPs) result in differences in the cellular composition and biomolecular characteristics.

    Purpose: To evaluate the cellular composition and the cytokine-release kinetics of PRP according to differences in the preparation protocols.

    Study Design: Controlled laboratory study.

    Methods: Five preparation procedures were performed for 14 healthy subjects, including 2 manual procedures (single-spin [SS] at 900g for 5 minutes; double-spin [DS] at 900g for 5 minutes and then 1500g for 15 minutes) and 3 methods with commercial kits (Arthrex ACP, Biomet GPS, and Prodizen Prosys). After evaluation of cellular composition, each preparation was divided into 4 aliquots and incubated for 1 hour, 24 hours, 72 hours, and 7 days for the assessment of cytokine release over time. The cytokine-release kinetics were evaluated by assessing platelet-derived growth factor (PDGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), interleukin-1 (IL-1), and matrix metalloproteinase-9 (MMP-9) concentrations of each aliquot with bead-based sandwich immunoassay.

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  • Point-Counterpoint: Is PRP Beneficial For Chronic Plantar Fasciitis?

    Plantar fasciosis is heel pain caused by deterioration of the plantar fascia, which occurs as a result of repetitive stress and chronic plantar fasciitis. This is the term used for the non-inflamed phase of plantar fasciopathy. It is much more difficult to treat plantar fasciosis when healthcare providers fail to recognize it as the non-inflamed phase of the condition.

    In plantar fasciitis, there is adequate blood supply to the problematic area as well as an inflammatory response that happens to be painful. In plantar fasciosis, the fascia has a decreased or absent inflammatory response, a reduction in the growth/healing factors, and chronic scar tissue that prevents the healing process.

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  • Effectiveness and safety of prolotherapy injections for management of lower limb tendinopathy and fasciopathy: a systematic review

    Abstract

    Introduction

    The aim of this review was to identify and evaluate existing research to determine the clinical effectiveness and safety of prolotherapy injections for treatment of lower limb tendinopathy and fasciopathy.

    Review

    Nine databases were searched (Medline, Science Direct, AMED, Australian Medical Index, APAIS-Health, ATSIhealth, EMBASE, Web of Science, OneSearch) without language, publication or data restrictions for all relevant articles between January 1960 and September 2014. All prospective randomised and non-randomised trials, cohort studies, case-series, cross-sectional studies and controlled trials assessing the effectiveness of one or more prolotherapy injections for tendinopathy or fasciopathy at or below the superior aspect of the tibia/fibula were included. Methodological quality of studies was determined using a modified evaluation tool developed by the Cochrane Musculoskeletal Injuries Group. Data analysis was carried out to determine the mean change of outcome measure scores from baseline to final follow-up for trials with no comparative group, and for randomised controlled trials, standardised mean differences between intervention groups were calculated. Pooled SMD data were calculated where possible to determine the statistical heterogeneity and overall effect for short-, intermediate- and long-term data. Adverse events were also reported.

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  • Leukocyte-Reduced Platelet-Rich Plasma Normalizes Matrix Metabolism in Torn Human Rotator Cuff Tendons

    Abstract

    Background: The optimal platelet-rich plasma (PRP) for treatment of supraspinatus tendinopathy has not been determined.

    Purpose: To evaluate the effect of low- versus high-leukocyte concentrated PRP products on catabolic and anabolic mediators of matrix metabolism in diseased rotator cuff tendons.

    Study Design: Controlled laboratory study.

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