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Background: Neurogenic thoracic outlet syndrome (NTOS) is a dynamic compression of the brachial plexus. This study aimed to evaluate the correlation between the concave deformity of the posterior edge of the anterior scalene muscle (CDAS) on sagittal T1 with intraoperative findings of vascular compression. The second aim was to define the NTOS vascular subtypes and establish possible treatments. Methods: We retrospectively reviewed patients who met the Consortium for Research and Education on Thoracic Outlet Syndrome criteria for NTOS and were operated on after a failed rehabilitation program. Results: Forty-four patients were included; mean age was 29.51 years (range: 13-55 years), and 24 (54.5%) were women. CDAS on sagittal T1 magnetic resonance imaging (MRI) was identified in 20 of 44. Patients were divided into two categories: type A (pure NTOS) (20 of 44); and type B (mixed neurogenic-vascular variants) (24 of 44). Type B was divided into B1, B2, and B3, corresponding to subclavian artery (SCA) compression (seven of 44), subclavian vein compression (SCV) (five of 44), and both SCA and SCV compression (12 of 44), respectively. All patients with B1 had CDAS on MRI T1 sagittal, whereas CDAS was found on 5%, 60%, and 58.3% in types A, B2, and B3, respectively. Intraoperatively, all patients had at least one structural anomaly. Preoperative symptoms of lower or middle-lower brachial plexus trunk compressions were more prominent in patients with the vascular variant (B1: 85%, B2: 83%, and B3: 83%) than the pure NTOS (type A) (40%). Conclusions: NTOS presents as four subtypes: pure neurogenic (A) and vascular (B1, B2, and B3). Preoperative middle/lower trunk symptoms combined with positive upper limb duplex ultrasound of the SCA, SCV, and sagittal MRI show that a CDAS is correlated with the vascular form of NTOS and predicts failure of preoperative rehabilitation program.
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PURPOSE: Estimation of glenoid bone loss in CT scans following shoulder dislocation is required to determine the type of surgery needed to restore shoulder stability. This paper presents a novel automatic method for the computation of glenoid bone loss in CT scans. METHODS: The model-based method is a pipeline that consists of four steps: (1) computation of an oblique plane in the CT scan that best matches the glenoid face orientation; (2) selection of the glenoid oblique CT slice; (3) computation of the circle that best fits the posteroinferior glenoid contour; (4) quantification of the glenoid bone loss. The best-fit circle is computed with newly defined Glenoid Clock Circle Constraints. RESULTS: The pipeline and each of its steps were evaluated on 51 shoulder CT scans (44 patients). Ground truth oblique slice, best-fit circle, and glenoid bone loss measurements were obtained manually from three clinicians. The full pipeline yielded a mean absolute error (%) for the bone loss deficiency of 2.3 ± 2.9 mm (4.67 ± 3.32%). The mean oblique CT slice selection difference was 1.42 ± 1.32 slices, above the observer variability of 1.74 ± 1.82 slices. The glenoid bone loss deficiency measure (%) on the ground truth oblique glenoid CT slice has a mean average error of 0.54 ± 1.03 mm (4.76 ± 3.00%), close to the observer variability of 0.93 ± 1.40 mm (2.98 ± 4.97%). CONCLUSION: Our pipeline is the first fully automatic method for the quantitative analysis of glenoid bone loss in CT scans. The computed glenoid bone loss report may assist orthopedists in selecting and planning surgical shoulder dislocation procedures.
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Instabilidade Articular , Luxação do Ombro , Articulação do Ombro , Humanos , Luxação do Ombro/diagnóstico por imagem , Luxação do Ombro/cirurgia , Articulação do Ombro/cirurgia , Instabilidade Articular/cirurgia , Escápula , Tomografia Computadorizada por Raios X/métodosRESUMO
Introduction: Post operative blood loss after reverse shoulder arthroplasty (RSA) is associated with the need for blood transfusion and prolonged hospital stay, among other complications. Tranexamic acid (TXA) reduces perioperative blood loss and is effective when delivered systemically or locally. We compared the effects of TXA on perioperative blood loss between elective and semi-urgent RSA. Methods: We retrospectively reviewed patients who underwent either elective or semi-urgent RSA for fracture repair, with and without TXA treatment. Demographics, clinical records, and laboratory results were collected and analyzed to compare peripheral blood hemoglobin concentrations before and after surgery, the need for blood transfusion, and length of hospital stay between the 2 groups. Results: In a cohort of 158 patients, 91 (58%) underwent elective RSA. TXA was administered in 91 (58%) patients from the entire group. TXA administration was associated with a significant decrease in post operative hemoglobin concentration reduction in both the elective and fracture groups (P = .026 and P = .018, respectively), a significant decrease in post operative blood transfusion rates (P = .004 and P = .003, respectively), and a decrease in the need for prolonged hospitalization (P = .038 and P = .009, respectively). Discussion: The local application of TXA during RSA yielded a significant reduction in perioperative blood loss. We showed a significant positive effect of local TXA administration during RSA that is comparable for both elective and semi-urgent patients. Due to the baseline characteristics of fracture patients, their clinical benefits may be more notable. Conclusions: The positive outcomes for surgical patients with the use of TXA during RSA can possibly cause future consideration in clinical practice.
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OBJECTIVES: To assess the status at 13 to 17â¯years follow-up of a cohort of young male traumatic shoulder dislocators. STUDY DESIGN: Prospective cohort study. METHODS: A prospective study of first-time young male traumatic shoulder dislocators, began in 2004. Subjects were evaluated by the apprehension test after completing rehabilitation 6 to 9â¯weeks post dislocation. Between March 2021 and July 2022, a telephone questionnaire was administered to ascertain their current shoulder status. Subjects were questioned about avoidance of activities of daily living and sport, participation in sports, current instability, and self-assessed shoulder function by the SANE score. RESULTS: 50/53 (94.3%) of the study subjects, mean age 20.4â¯years, completed a mean follow-up of 181.8⯱â¯12â¯months. The non-redislocation survival was 13% for those with a positive apprehension test and 49% for those with a negative test (pâ¯=â¯0.007). SANE scores were 64.3⯱â¯23.7 for those with a positive apprehension test and 83.7⯱â¯19.7 for those with a negative test (pâ¯=â¯0.001). In the year before the follow-up, 33.3% of those treated conservatively and 42.9% treated surgically experienced subluxation (pâ¯=â¯0.5). Fifty-seven percent of those who were treated conservatively and 56% of those who underwent surgery avoided some ADL or sports because of their shoulder. CONCLUSIONS: For young male first time traumatic shoulder dislocators a positive apprehension test after rehabilitation is associated with a high risk for reoccurrence and poorer long-term results. Most subjects were still dealing with shoulder symptoms at long-term follow-up.
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Luxações Articulares , Instabilidade Articular , Luxação do Ombro , Articulação do Ombro , Humanos , Masculino , Adulto Jovem , Adulto , Luxação do Ombro/diagnóstico , Luxação do Ombro/cirurgia , Seguimentos , Ombro , Estudos Prospectivos , Atividades Cotidianas , Instabilidade Articular/diagnóstico , Recidiva , Artroscopia , Estudos RetrospectivosRESUMO
BACKGROUND: Anterior shoulder instability is typically characterized by detachment of the anteroinferior labrum (Bankart lesion). Some patients also sustain a superior labrum anterior-to-posterior (SLAP) injury. The purpose of this study was to compare the medium-term clinical results of isolated anterior Bankart repairs (ABR) with those of combined Bankart and SLAP repair (ABR + SLAP). METHODS: Data on all patients treated surgically for recurrent anterior shoulder instability between 2006 and 2011 were retrospectively collected from medical charts. The minimum follow-up was 5 years. Patients were interviewed to assess patient-reported outcome measurements (PROM) as determined by the American Shoulder and Elbow Surgeons Score (ASES), the Subjective Shoulder Score (SSV), and the Disabilities of the Arm, Shoulder, and Hand Score (DASH), as well as their quality of life (QOL: SF12 questionnaire). Information on complications, re-operations, and recurrent instability was recorded and evaluated as well. RESULTS: A total of 150 patients (88% males) with a mean age 23.7 years (range 15-40) were included. Forty-two patients following ABR + SLAP repair were compared to 108 patients following ABR alone, with a mean follow-up of 7.8 years (range 5-10.7). The rate of re-dislocation was similar in both groups (26% for ABR + SLAP vs 20% for ABR, p = .44). There were no significant differences in functional outcome between the ABR + SLAP and the ABR alone groups (SSV 86.7 vs 86.5, p = .93, ASES 89.6 vs 86.5, p = .11, and DASH 4.9 vs 7, p = .17), or in QOL outcome (SF12 physical 95.6 vs 93.3, p = .27, SF12 mental 84.4 vs 85.7, p = .63). CONCLUSION: Surgical repair for anterior shoulder instability and a coexisting SLAP lesion yields clinical results as good as those of isolated ABR, as evidenced by similar PROM and re-dislocation rates after medium-term follow-up. LEVEL OF EVIDENCE: III.
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Luxações Articulares , Instabilidade Articular , Luxação do Ombro , Articulação do Ombro , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Feminino , Luxação do Ombro/complicações , Articulação do Ombro/cirurgia , Qualidade de Vida , Seguimentos , Estudos Retrospectivos , Instabilidade Articular/etiologia , Artroscopia/métodos , Luxações Articulares/etiologia , Medidas de Resultados Relatados pelo Paciente , RecidivaRESUMO
BACKGROUND: For most patients, tennis elbow (TE) resolves within 6 months of onset. For those with persistent and painful TE, nonsurgical treatment options are limited. Thousands of studies have tried to find effective treatments for TE but have usually failed. In this study, we tested the hypothesis that injections with hyaluronic acid (HA) would be effective at reducing pain from chronic TE. METHODS: Patients with a minimum of six months of pain from TE and with a pain level of 50 or greater (out of 100) were included in the study. They were randomized equally into one of two treatment groups: injection with HA or injection with saline control. Follow-up was conducted at 3, 6 and 12 months from the initial injection. Both the patient and the examiner at the follow-up visits were blinded to the treatment arm. The primary outcome measure was the visual analog scale (VAS pain) score at one year. Additional outcome measures included the shortened Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) and Patient Rated Tennis Elbow Evaluation (PRTEE) scores. RESULTS: Eighteen patients were randomized into the HA injection treatment arm, and 17 (94%) completed the study. The average age was 51.9 years, and 10 of the subjects were male. Patients had an average of 28.1 months of pain before entering the study. The VAS score in the HA group decreased from a baseline of 76.4-14.3 at 12 months. All 17 patients in the HA group showed VAS score reductions above the minimal clinically important difference (MCID) of at least 18. The PRTEE score improved from 67 to 28.1. The QuickDASH score improved from 53.7 to 22.5. Follow-up in the saline group was less than 50% and was therefore not used as a comparator. CONCLUSIONS: HA injections yielded significant success in pain relief by three months. Patients continued to improve for the 12-month duration of the study. This study indicates that patients with chronic lateral epicondylitis may benefit from receiving injections of hyaluronic acid rather than having to undergo surgery.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Artrite Infecciosa/diagnóstico , Manguito Rotador , Articulação do Ombro , Dor de Ombro , Tendinopatia , Sedimentação Sanguínea , Proteína C-Reativa/análise , Calcinose/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Contagem de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/patologia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/patologia , Dor de Ombro/diagnóstico , Dor de Ombro/tratamento farmacológico , Dor de Ombro/etiologia , Tendinopatia/sangue , Tendinopatia/diagnóstico , Tendinopatia/tratamento farmacológico , Tendinopatia/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Despite the existence of potent anti-inflammatory biological drugs e.g., anti-TNF and anti IL-6 receptor antibodies, for treating chronic inflammatory and autoimmune diseases, these are costly and not specific. Cheaper oral available drugs remain an unmet need. Expression of the acute phase protein Serum Amyloid A (SAA) is dependent on release of pro-inflammatory cytokines IL-1, IL-6 and TNF-α during inflammation. Conversely, SAA induces pro-inflammatory cytokine secretion, including Th17, leading to a pathogenic vicious cycle and chronic inflammation. 5- MER peptide (5-MP) MTADV (methionine-threonine-alanine-aspartic acid-valine), also called Amilo-5MER, was originally derived from a sequence of a pro-inflammatory CD44 variant isolated from synovial fluid of a Rheumatoid Arthritis (RA) patient. This human peptide displays an efficient anti-inflammatory effects to ameliorate pathology and clinical symptoms in mouse models of RA, Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). Bioinformatics and qRT-PCR revealed that 5-MP, administrated to encephalomyelytic mice, up-regulates genes contributing to chronic inflammation resistance. Mass spectrometry of proteins that were pulled down from an RA synovial cell extract with biotinylated 5-MP, showed that it binds SAA. 5-MP disrupted SAA assembly, which is correlated with its pro-inflammatory activity. The peptide MTADV (but not scrambled TMVAD) significantly inhibited the release of pro-inflammatory cytokines IL-6 and IL-1ß from SAA-activated human fibroblasts, THP-1 monocytes and peripheral blood mononuclear cells. 5-MP suppresses the pro-inflammatory IL-6 release from SAA-activated cells, but not from non-activated cells. 5-MP could not display therapeutic activity in rats, which are SAA deficient, but does inhibit inflammations in animal models of IBD and MS, both are SAA-dependent, as shown by others in SAA knockout mice. In conclusion, 5-MP suppresses chronic inflammation in animal models of RA, IBD and MS, which are SAA-dependent, but not in animal models, which are SAA-independent.
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Artrite Reumatoide/imunologia , Receptores de Hialuronatos/genética , Inflamação/imunologia , Doenças Inflamatórias Intestinais/imunologia , Esclerose Múltipla/imunologia , Peptídeos/genética , Proteína Amiloide A Sérica/imunologia , Animais , Anti-Inflamatórios/uso terapêutico , Autoimunidade , Células Cultivadas , Biologia Computacional , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Knockout , Peptídeos/uso terapêutico , Proteína Amiloide A Sérica/genéticaRESUMO
CASE: A 16-year-old girl presented with pain and swelling of the medial edge of the clavicle. She denied previous trauma and was evaluated by multiple physicians for a possible infection or neoplastic lesion. The patient underwent multiple studies and procedures, including blood tests, imaging studies, and biopsy. After 6 months, a diagnosis of osteochondrosis of the medial clavicle was made. After 1 year of observation, the symptoms resolved. CONCLUSIONS: The rarity of Friedrich disease and the scarcity of literature may lead to delayed diagnosis of this pathology. Awareness of medical personnel of this condition may facilitate accurate diagnosis.
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Clavícula/diagnóstico por imagem , Osteonecrose/diagnóstico por imagem , Articulação Esternoclavicular/diagnóstico por imagem , Adolescente , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Regenerative medicine research has evolved significantly in recent years. There is a great un-met clinical need for developing new treatments that will induce regeneration of injured skeletal tissues in cases such as large bony defects caused by trauma or tumor resection, articular cartilage defects and torn or degenerate tendons and ligaments. Except for bone that can regenerate small defects, all other skeletal tissues do not hold the natural capability for regeneration after injury and rather form a less functional scar tissue. In order to induce tissue regeneration, it is now believed that three crucial elements must reach the injured zone: a) multipotent cells that can rapidly proliferate and differentiate to form the injured tissues, such as mesenchymal stem cells for skeletal tissues; b) extra-cellular matrix that will support the newly built tissues, and c) the correct molecular signals. Using diverse research tools and expertise, our department focused its research on basic, translational and clinical solutions for injured and degenerative skeletal tissues. In this review we will describe our different research directions, from in-vitro cell cultures and animal models studies to human clinical trials.
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Regeneração Óssea/fisiologia , Medicina Regenerativa , Animais , Osso e Ossos , Cartilagem , Modelos Animais de Doenças , Humanos , Células-Tronco Mesenquimais , Modelos Biológicos , Transplante de Células-TroncoRESUMO
Synovial lipomatosis (also known as lipoma arborescens) is a rare and benign lesion affecting synovium-lined cavities. It is characterized by hyperplasia of mature fat tissue in the subsynovial layer. Although the most commonly affected site is the knee joint, rarely additional locations such as tendon sheath and other joints are involved. We present a case of synovial lipomatosis of the glenohumeral joint in a 44-year-old man. The clinical data radiological studies and histopathologic results are described, as well as a review of the current literature.
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Cigarette smoking is associated with musculoskeletal degenerative disorders, delayed fracture healing, and nonunion. Bone marrow progenitor cells (BMPCs), known to express CD105, are important in local trophic and immunomodulatory activity and central to musculoskeletal healing/regeneration. We hypothesized that smoking is associated with lower levels of BMPC. Iliac bone marrow samples were collected from individuals aged 18-65 years during the first steps of pelvic surgery, under IRB approval with informed consent. Patients with active infectious or neoplastic disease, a history of cytotoxic or radiation therapy, primary or secondary metabolic bone disease, or bone marrow dysfunction were excluded. Separation process purity and the number of BMPCs recovered were assessed with FACS. BMPC populations in self-reported smokers and nonsmokers were compared using the two-tailed t-test. 13 smokers and 13 nonsmokers of comparable age and gender were included. The average concentration of BMPCs was 3.52 × 10(5)/mL ± 2.45 × 10(5)/mL for nonsmokers versus 1.31 × 10(5)/mL ± 1.61 × 10(5)/mL for smokers (t = 3.2, P = 0.004). This suggests that cigarette smoking is linked to a significant decrease in the concentration of BMPCs, which may contribute to the reduced regenerative capacity of smokers, with implications for musculoskeletal maintenance and repair.
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BACKGROUND: Proximal humeral locking plates have significantly improved the treatment of proximal humeral fractures in recent years; however, they are not devoid of complications. Inadvertent screw penetration into the joint is a well-documented complication. Intraoperative 3-dimensional (3D) imaging may assist in detecting intra-articular implant penetration. This study compared the performance of a standard C-arm fluoroscope with a novel 3D imaging fluoroscope in detecting penetrating implants in a proximal humeral fracture model. METHODS: Zinc-sprayed proximal humerus sawbones were affixed with a proximal humeral locking plate. Six different constructs were assembled. In each specimen, 1 screw, 2 screws, or no screws were inserted 2-mm proud of the articular surface. Each specimen was imaged with a conventional fluoroscope and a 3D imaging fluoroscope. Overall, 36 image sets were prepared for each modality. These were evaluated by 2 fellowship-trained surgeons for intraobserver and interobserver reliability as well for the accuracy of detecting prominent implants in the 2 imaging methods. RESULTS: Overall accuracy for observer A was 89.9% compared with 100% for C-arm fluoroscopy and 3D imaging fluoroscopy (P < .01) and for observer B was 91.1% and 100% (P = .01), respectively. The κ values were 0.74 with C-arm fluoroscopy and 1.0 for the 3D imaging fluoroscopy for observer A, and 0.93 and 1.0, respectively, for observer B. CONCLUSIONS: In a proximal humeral fracture model, C-arm fluoroscopy is a highly accurate imaging modality that can minimize the incidence of penetrating screws into the joint. Further clinical studies are required to establish this modality.
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Parafusos Ósseos , Fluoroscopia , Fixação Interna de Fraturas/efeitos adversos , Cabeça do Úmero/diagnóstico por imagem , Fraturas do Ombro/cirurgia , Placas Ósseas , Fixação Interna de Fraturas/instrumentação , Humanos , Cabeça do Úmero/cirurgia , Imageamento Tridimensional , Complicações Intraoperatórias/diagnóstico por imagem , Modelos Anatômicos , Reprodutibilidade dos TestesRESUMO
Distal tibial fractures tend towards delayed- or nonunion. The purpose of this study was to evaluate the safety and efficacy of early minimally invasive intervention (MII) in the treatment of these fractures. A total 24 consecutive patients who underwent operative treatment for distal tibial fractures were randomized into a control and an intervention group. MII entailed aspirating iliac crest bone marrow and peripheral blood, yielding mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) respectively, that were mixed with demineralized bone matrix (DBM) and injected under fluoroscopic control into the fracture site. No complications occurred in either group. The median time to union was 1.5 months in the MII group and 3 months in the control group. MII was found to be a safe and efficient procedure.
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Terapia Baseada em Transplante de Células e Tecidos , Fraturas não Consolidadas/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Adolescente , Adulto , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Feminino , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Bone is an obvious candidate tissue for stem cell therapy. This review provides an update of existing stem cell-based clinical treatments for bone pathologies. SOURCES OF DATA: A systematic computerized literature search was conducted. The following databases were accessed on 10 February 2011: NIH clinical trials database, PubMed, Ovid and Cochrane Reviews. AREAS OF AGREEMENT: Stem cell therapy offers new options for bone conditions, both acquired and inherited. AREAS OF CONTROVERSY: There is still no agreement on the exact definition of 'mesenchymal stem cells'. Consequently, it is difficult to appreciate the effect of culture expansion and the feasibility of allogeneic transplantation. GROWING POINTS: Based on the sound foundations of pre-clinical research, stem cell-based treatments and protocols have recently emerged. AREAS TIMELY FOR DEVELOPING RESEARCH: Well-designed prospective clinical trials are needed in order to establish and develop stem cell therapy for bone diseases.
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Doenças Ósseas/terapia , Osso e Ossos/fisiologia , Consolidação da Fratura/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Osteogênese/fisiologia , Doenças Ósseas/etiologia , Doenças Ósseas/patologia , Regeneração Óssea/fisiologia , Osso e Ossos/patologia , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco Mesenquimais/tendências , Medicina Regenerativa/métodos , Medicina Regenerativa/tendências , Pesquisa com Células-TroncoRESUMO
OBJECTIVE: Mesenchymal stem cells (MSCs) are multipotent cells that are capable of differentiating into multilineages of the mesenchyme. MSCs were shown to have immune-modulating properties in vitro and were successfully used in vivo for controlling graft-versus-host disease, skin rejection, and modulation of inflammation. Our previous study suggested that human MSCs (hMSCs) block antigen-presenting cell (APC) maturation in a contact-dependent manner as well as induce the expression of the anti-inflammatory cytokine, interleukin-10 (IL-10). However, the molecular mechanisms that block initiation of immune responses by MSCs remains to be investigated. METHODS: A coculture system of hMSCs and APCs was used to study Signal Transducer and Activators of Transcription-3 (STAT3) activation using nonradioactive STAT3 transcription factor assay, flow cytometric immunostaining, and Western blotting. RESULTS: We show that the transcription factor STAT3 is constitutively activated in hMSCs, and upon coculturing with APCs, there is a significant increase in its activity in both cell types. This increase in STAT3 activity is independent of soluble factor(s) and requires cell-cell contact. Importantly, blocking STAT3 signaling in the APCs by specific inhibitors resulted in reduced IL-10 expression and reversal of hMSC-mediated inhibition of proinflammatory cytokines. CONCLUSION: These findings suggest that APC's STAT3 plays a key role in mediating the immunomodulatory effects of hMSCs. Moreover, the induction of STAT3 signaling by hMSCs is mediated by a novel mechanism involving cell-cell interaction rather than the classical mechanism of induction by cytokines.
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Células Apresentadoras de Antígenos/imunologia , Comunicação Celular/imunologia , Células-Tronco Mesenquimais/imunologia , Fator de Transcrição STAT3/imunologia , Transdução de Sinais/imunologia , Células Apresentadoras de Antígenos/citologia , Células Cultivadas , Técnicas de Cocultura , Humanos , Interleucina-10/biossíntese , Células-Tronco Mesenquimais/citologiaRESUMO
Infusion of either embryonic or mesenchymal stem cells prolongs the survival of organ transplants derived from stem cell donors and prevents graft-versus-host-disease (GVHD). An in-depth mechanistic understanding of this tolerization phenomenon could lead to novel cell-based therapies for transplantation. Here we demonstrate that while human mesenchymal stem cells (hMSCs) can promote superantigen-induced activation of purified T cells, addition of antigen-presenting cells (APCs; either monocytes or dendritic cells) to the cultures inhibits the T-cell responses. This contact- and dose-dependent inhibition is accompanied by secretion of large quantities of interleukin (IL)-10 and aberrant APC maturation, which can be partially overridden by the addition of factors that promote APC maturation (ie, lipopolysaccharide [LPS] or anti-CD40 monoclonal antibody [mAb]). Thus, our data support an immunoregulatory mechanism wherein hMSCs inhibit T cells indirectly by contact-dependent induction of regulatory APCs with T-cell-suppressive properties. Our data may reveal a physiologic phenomenon whereby the development of a distinct APC population is regulated by the tissue's cellular microenvironment.