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Recent studies have suggested that therapies with stem cells and amniotic membrane can modulate the inflammation following an ischemic injury in the heart. This study evaluated the effects of bone-marrow mononuclear cells (BMMC) and acellular human amniotic membrane (AHAM) on cardiac function and NLRP3 complex in a rat model of heart failure.On the 30th day,the echocardiographic showed improvements on ejection fraction and decreased pathological ventricular remodeling on BMMC and AHAM groups.Oxidative stress analysis was similar between the three groups,and the NLRP3 inflammasome activity were not decreased with the therapeutic use of both BMMC and AHAM,in comparison to the control group.
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Insuficiencia Cardíaca , Inflamasomas , Humanos , Animales , Ratas , Proteína con Dominio Pirina 3 de la Familia NLR , Amnios , Médula ÓseaRESUMEN
This study aims to evaluate and compare cellular therapy with human Wharton's jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund's complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 × 105. Moreover, the cells were placed in a 10 µL solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases.
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Encefalomielitis Autoinmune Experimental , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Esclerosis Múltiple , Animales , Encefalomielitis Autoinmune Experimental/terapia , Encefalomielitis Autoinmune Experimental/patología , Ratas , Esclerosis Múltiple/terapia , Esclerosis Múltiple/patología , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Humanos , Femenino , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Células-Madre Neurales , Modelos Animales de Enfermedad , Gelatina de Wharton/citologíaRESUMEN
The treatment of tracheal pathologies remains challenging.Nanotechnology allows adding substances to decellularized human amniotic membrane (DHAM), such as 15-Deoxy-∆12,14ProstaglandinJ2 nanoparticles (15D-PGJ2-NC).This study performed a tracheotomy in rabbits randomized into three groups.The tissue repair process was evaluated when treated with DHAM associated or not with 15D-PGJ2-NC.The average of the area in the control group was 54.76% smaller than DHAM group and 41.98% smaller than DHAM + 15D-PGJ2-NC group (p=0.004 for both).The DHAM + 15D-PGJ2-NC group had significantly more immature cartilage (p=0.015).DHAM impregnated with 15D-PGJ2-NC could provide support for the healing of the tracheal defect and may prevent reduction of its lumen.
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Amnios , Nanopartículas , Animales , Conejos , Humanos , Endotelio Vascular , Matriz Extracelular , Cicatrización de HeridasRESUMEN
Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function.
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Apoptosis , Corazón/fisiología , Células Madre Multipotentes/fisiología , Infarto del Miocardio/cirugía , Células Madre Pluripotentes/fisiología , Regeneración/fisiología , Animales , Bioingeniería/métodos , Supervivencia Celular , Exosomas/metabolismo , Terapia Genética , Humanos , Precondicionamiento Isquémico Miocárdico , MicroARNs/fisiología , Células Madre Multipotentes/trasplante , Infarto del Miocardio/patología , Miocitos Cardíacos/patología , Células Madre Pluripotentes/trasplante , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Tracheal grafts have been investigated for over a century, aiming to replace various lesions. However, tracheal reconstruction surgery remains a challenge, primarily due to anatomical considerations, intraoperative airway management, the technical complexity of reconstruction, and the potential postoperative morbidity and mortality. Due to research development, the amniotic membrane (AM) and Wharton's Jelly (WJ) arise as alternatives within the new set of therapeutic alternatives. These structures hold significant therapeutic potential for tracheal defects. This study analyzed the capacity of tracheal tissue regeneration after 60 days of decellularized WJ and AM implantation in rabbits submitted to conventional tracheostomy. METHODS: An in vivo experimental study was carried out using thirty rabbits separated into three groups (Control, AM, and WJ) (n = 10). The analyses were performed 60 days after surgery through immunohistochemistry. RESULTS: Different immunomarkers related to scar regeneration, such as aggrecan, TGF-ß1, and α-SMA, were analyzed. However, they highlighted no significant difference between the groups. Collagen type I, III, and Aggrecan also showed no significant difference between the groups. CONCLUSIONS: Both scaffolds appeared to be excellent frameworks for tissue engineering, presenting biocompatibility and a desirable microenvironment for cell survival; however, they did not display histopathological benefits in trachea tissue regeneration.
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BACKGROUND: Previous studies suggested that transplantation of autologous bone marrow-derived mononuclear cells (BMNCs) improves heart function in chronic chagasic cardiomyopathy. We report the results of the first randomized trial of BMNC therapy in chronic chagasic cardiomyopathy. METHODS AND RESULTS: Patients 18 to 75 years of age with chronic chagasic cardiomyopathy, New York Heart Association class II to IV heart failure, left ventricular ejection fraction (LVEF) <35, and optimized therapy were randomized to intracoronary injection of autologous BMNCs or placebo. The primary end point was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5. Between July 2005 and October 2009, 234 patients were enrolled. Two patients abandoned the study and 49 were excluded because of protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had a trimmed mean age of 52.4 years (range, 50.8-54.0 years) and LVEF of 26.1 (range, 25.1-27.1) at baseline. Median number of injected BMNCs was 2.20×10(8) (range, 1.40-3.50×10(8)). Change in LVEF did not differ significantly between treatment groups: trimmed mean change in LVEF at 6 months, 3.0 (1.3-4.8) for BMNCs and 2.5 (0.6-4.5) for placebo (P=0.519); change in LVEF at 12 months, 3.5 (1.5-5.5) for BMNCs and 3.7 (1.5-6.0) for placebo (P=0.850). Left ventricular systolic and diastolic volumes, New York Heart Association functional class, Minnesota quality-of-life questionnaire, brain natriuretic peptide concentrations, and 6-minute walking test did also not differ between groups. CONCLUSION: Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with chronic chagasic cardiomyopathy.
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Trasplante de Médula Ósea/métodos , Cardiomiopatía Chagásica/terapia , Calidad de Vida , Función Ventricular Izquierda , Adolescente , Adulto , Anciano , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Actividad Motora , Trasplante Autólogo , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Most transplanted organs are obtained from brain-dead donors. Inflammation results in a higher rate of rejection. Objectives: The objective of this animal model of brain death (BD) was to evaluate the effect of the progressive institution of volume expansion, norepinephrine, and combined hormone therapy on clinical, laboratory, and histological aspects. Methods: Twenty rabbits were divided: A (control), B (induction of BD + infusion of crystalloid), C (BD + infusion of crystalloid and noradrenaline (NA)), and D (BD + infusion of crystalloid + vasopressin + levothyroxine + methylprednisolone + NA). The animals were monitored for four hours with consecutives analysis of vital signs and blood samples. The organs were evaluated by a pathologist. Results: In Group D, we observed fewer number and lesser volume of infusions (p = 0.032/0.014) when compared with groups B and C. Mean arterial pressure levels were higher in group D when compared with group B (p = 0.008). Group D had better glycemic control when compared with group C (p = 0.016). Sodium values were elevated in group B in relation to groups C and D (p = 0.021). In Group D, the organ perfusion was better. Conclusion: The optimized strategy of management of BD animals is associated with better hemodynamic, glycemic, and natremia control, besides reducing early signs of ischemia.
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Background: Post-procedure residual ischemia is associated with worse prognosis in patients with coronary artery diasease (CAD). Objective: We evaluated whether autologous bone marrow-derived cells (BMC) contribute to additional reduction in regional stress-induced myocardial ischemia (SIMI) in patients undergoing incomplete coronary artery bypass graft surgery (CABG). Methods: In a double-blind, randomized, placebo-controlled trial, we enrolled 143 patients (82% men, 58 ± 11 years) with stable CAD and not candidates for complete CABG. They received 100 million BMC (n = 77) or placebo (n = 66) injected into ischemic non-revascularized segments during CABG. The primary outcome was improvement on SIMI quantified as the area at risk in injected segments assessed by cardiovascular magnetic resonance (CMR) 1, 6, and 12 months after CABG. Results: The reduction in global SIMI after CABG was comparable (p = 0.491) in both groups indicating sustained beneficial effects of the surgical procedure over 12 month period. In contrast, we observed additional improvement in regional SIMI in BMC treated group (p = 0.047). Baseline regional SIMI values were comparable [18.5 (16.2-21.0) vs. 18.5 (16.5-20.7)] and reached the lowest values at 1 month [9.74 (8.25; 11.49) vs. 12.69 (10.84; 14.85)] for BMC and placebo groups, respectively. The ischemia's improvement from baseline represented a 50% difference in regional SIMI in favor of the BMC transplanted group at 30 days. We found no differences in clinical and LVEF% between groups during the 12 month follow-up period. The 1 month rate of major adverse cerebral and cardiovascular events (MACCE) (p = 0.34) and all-cause mortality (p = 0.08) did not differ between groups 1 month post intervention. Conclusion: We provided evidence that BMC leads to additional reduction in regional SIMI in chronic ischemic patients when injected in segments not subjected to direct surgical revascularization. This adjuvant therapy deserves further assessment in patients with advanced CAD especially in those with microcirculation dysfunction. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT01727063.
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Wound healing is a complex process of repair that involves the interaction between different cell types and involves coordinated interactions between intracellular and extracellular signaling. Bone Marrow Mesenchymal Stem Cells (BMSCs) based and acellular amniotic membrane (AM) therapeutic strategies with the potential for treatment and regeneration of tissue. We aimed to evaluate the involvement of paracrine effects in tissue repair after the flap skin lesion rat model. In the full-thickness flap skin experiment of forty Wistar rats: A total of 40 male Wistar rats were randomized into four groups: group I: control (C; n = 10), with full-thickness lesions on the back, without (BMSCs) or AM (n = 10); group II: injected (BMSCs; n = 10); group III: covered by AM; group IV-injected (AM + BMSCs; n = 10). Cytokine levels, IL-1, and IL-10 assay kits, superoxide dismutase (SOD), glutathione reductase (GRs) and carbonyl activity levels were measured by ELISA 28th day, and TGF-ß was evaluated by immunohistochemical, the expression collagen expression was evaluated by Picrosirius staining. Our results showed that the IL-1 interleukin was higher in the control group, and the IL-10 presented a higher mean when compared to the control group. The groups with BMSCs and AM showed the lowest expression levels of TGF-ß. SOD, GRs, and carbonyl activity analysis showed a predominance in groups that received treatment from 80%. The collagen fiber type I was predominant in all groups; however, the AM + BMSCs group obtained a higher average when compared to the control group. Our findings suggest that the AM+ BMSCs promote skin wound healing, probably owing to their paracrine effect attributed to the promotion of new collagen for tissue repair.
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OBJECTIVE: To compare models of the postoperative hospital treatment phase after myocardial revascularization. DESIGN: A pilot randomized controlled trial. SETTING: Hospital patients in a hospital setting. SUBJECTS: Thirty-two patients with indications for myocardial revascularization were included between January 2008 and December 2009, with a left ventricular ejection fraction (LVEF) ≥50%, 1-second forced expiratory volume (FEV(1)) ≥60 and forced vital capacity (FVC) ≥60% of predicted value. INTERVENTIONS: Patients were randomly placed into two groups: one performed prescribed exercises according to the model proposed by the American College of Sports Medicine (ACSM) and the other according to a periodized model. MAIN MEASURES: Partial pressure of O(2) (P o (2)) and arterial O(2) saturation (Sao (2)), percentage of predicted FVC and total distance on the six-minute walking test (6MWT). RESULTS: Twenty-seven patients were re-evaluated upon release from the hospital (ACSM = 14 and PP = 13). Five patients extubated for more than 6 hours in the postoperative period were excluded from the sample. In the preoperative period the variables P o (2), Sao (2), % FVC and 6MWT were similar. In the postoperative period, a reduction was observed for all parameters in both groups. Upon comparison of the groups, a difference was observed in P o (2) (ACSM = 68.0 ± 4.3 vs. PP = 75.9 ± 4.8 mmHg; P < 0.001), Sao (2) (ACSM = 93.5 ± 1.4 vs. PP = 94.8 ± 1.2%; P = 0.018) and 6MWT (ACSM = 339.3 ± 41.7 vs. PP = 393.8 ± 25.7 m; P < 0.001). There was no difference in % FVC. CONCLUSION: Patients after myocardial revascularization following a periodized model of exercise presented a better intra-hospital evolution when compared to those using the ACSM model.
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Terapia por Ejercicio/métodos , Tolerancia al Ejercicio , Revascularización Miocárdica/rehabilitación , Anciano , Brasil , Humanos , Pacientes Internos , Persona de Mediana Edad , Consumo de Oxígeno/fisiología , Proyectos Piloto , Periodo Posoperatorio , Espirometría , Resultado del Tratamiento , Capacidad Vital/fisiología , Caminata/fisiologíaRESUMEN
Most injuries in the hand and fingers, especially on the digital pulps, are suited for healing by secondary intention. Nevertheless, delay in epithelization seems to unfavorably restrict this technique. The purpose of this controlled randomized clinical trial is to analyze by means of photo planimetry the progression of the healing process by secondary intention in acute wounds of the hand using the standardized extract of Calendula officinalis L. (SEC). The cohort of eligible participants included two groups of 20 patients with skin loss in the hand and fingers treated by secondary intention. Control group (CG) used mineral oil and intervention group (IG) received SEC. Wound pictures were captured at each outpatient assessment until epithelization was achieved and measured with ImageJ. Intervention group (IG) and control group (CG) with 19 wounds each, primarily formed by men in their 40's with wounds in their index and ring fingers on the left side, showed homogeneous variables and similar initial wound areas. Epithelization time was shorter and healing speed was faster in IG (IG = 8.6 ± 4.7 days and 9.5 ± 5.8%day versus CG = 13.2 ± 7.4 days and 6.2 ± 2.9%day, Æ¿ < 0.05), leading to the conclusion that healing by secondary intention in acute wounds of the hand and fingers with SEC led to a faster epithelization.
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Calendula , Humanos , Masculino , Extractos Vegetales/uso terapéutico , Cicatrización de HeridasRESUMEN
BACKGROUND: Reduction of LDL-cholesterol (LDL-c) levels is the cornerstone in risk reduction, but many high-risk patients are not achieving the recommended lipid goals, even in high-income countries. OBJECTIVE: To evaluate whether patients seen in the city of Curitiba public health system are reaching LDL-c goals after an acute myocardial infarction (AMI). METHODS: This retrospective cohort explored the data of patients admitted with AMI between 2008 and 2015 in public hospitals from the city of Curitiba. In order to evaluate the attainment of the LDL-c target, we have used the last value registered in the database for each patient up to 2016. For those who had at least one LDL-c registered in the year before AMI, percentage of reduction was calculated. The level of significance adopted for statistical analysis was p<0.05. RESULTS: Of 7,066 patients admitted for AMI, 1,451 were followed up in an out-patient setting and had at least one evaluation of LDL-c. Mean age was 60.8±11.4 years and 35.8%, 35.2%, 21.5%, and 7.4% of patients had LDL-c levels ≥100, 70-99, 50-69 and <50 mg/dL, respectively. Of these, 377 patients also had at least one LDL-c evaluation before the AMI. Mean LDL-c concentrations were 128.0 and 92.2 mg/dL before and after AMI, with a mean reduction of 24.3% (35.7 mg/dL). LDL-c levels were reduced by more than 50% in only 18.3% of the cases. CONCLUSION: In the city of Curitiba public health system patients, after myocardial infarction, are not achieving adequate LDL-c levels after AMI.
FUNDAMENTO: A redução dos níveis de colesterol LDL é a pedra angular na redução de risco, mas muitos pacientes de alto risco não estão atingindo as metas lipídicas recomendadas, mesmo em países de alta renda. OBJETIVO: Avaliar se os pacientes atendidos na rede pública de saúde da cidade de Curitiba estão atingindo as metas de colesterol LDL após infarto agudo do miocárdio (IAM). MÉTODOS: Esta coorte retrospectiva explorou os dados de pacientes internados com IAM entre 2008 e 2015 em hospitais públicos da cidade de Curitiba. Para avaliar o atingimento da meta de colesterol LDL, utilizamos o último valor registrado no banco de dados para cada paciente até o ano de 2016. Para aqueles que tinham pelo menos um valor de colesterol LDL registrado no ano anterior ao IAM, calculou-se o percentual de redução. O nível de significância adotado para a análise estatística foi p<0,05. RESULTADOS: Dos 7.066 pacientes internados por IAM, 1.451 foram acompanhados em ambiente ambulatorial e tiveram pelo menos uma avaliação de colesterol LDL. A média de idade foi 60,8±11,4 anos e 35,8%, 35,2%, 21,5% e 7,4% dos pacientes apresentavam níveis de colesterol LDL≥100, 7099, 5069 e <50 mg/dL, respectivamente. Destes, 377 pacientes também tiveram pelo menos uma avaliação de colesterol LDL antes do IAM. As concentrações médias de colesterol LDL foram 128,0 e 92,2 mg/dL antes e após o IAM, com redução média de 24,3% (35,7 mg/dL). Os níveis de colesterol LDL foram reduzidos em mais de 50% em apenas 18,3% dos casos. CONCLUSÃO: Na cidade de Curitiba, pacientes do sistema público de saúde, após infarto do miocárdio, não estão atingindo níveis adequados de colesterol LDL após IAM.
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Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized as an inflammatory demyelinating disease. Given the need for improvements in MS treatment, many studies are mainly conducted through preclinical models such as experimental allergic encephalomyelitis (EAE). This study analyzes the relationships between histopathological and clinical score findings at EAE. Twenty-three female Rattus norvegicus Lewis rats from 6 to 8 weeks were induced to EAE. Nineteen rats underwent EAE induction distributed in six groups to establish the evolution of clinical signs, and four animals were in the control group. Bordetella pertussis toxin (PTX) doses were 200, 250, 300, 350 and 400 ng. The clinical scores of the animals were analyzed daily, from seven to 24 days after induction. The brains and spinal cords were collected for histopathological analyses. The results demonstrated that the dose of 250 ng of PTX induced a higher clinical score and reduction in weight. All induced groups demonstrated leukocyte infiltration, activation of microglia and astrocytes, and demyelinated plaques in the brains in histopathology. It was concluded that the dose of 250 ng and 350 ng of PTX were the best choices to trigger the brain and spinal cord demyelination lesions and did not correlate with clinical scores.
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BACKGROUND: Tracheal lesions are pathologies derived from the most diverse insults that can result in a fatal outcome. Despite the number of techniques designed for the treatment, a limiting factor is the extent of the extraction. Therefore, strategies with biomaterials can restructure tissues and maintain the organ's functionality, like decellularized Wharton's jelly (WJ) as a scaffold. The aim is to analyze the capacity of tracheal tissue regeneration after the implantation of decellularized WJ in rabbits submitted to a tracheal defect. METHODS: An in vivo experimental study was undertaken using twenty rabbits separated into two groups (n = 10). Group 1 submitted to a tracheal defect, group 2 tracheal defect, and implantation of decellularized WJ. The analyses were performed 30 days after surgery through immunohistochemistry. RESULTS: Inner tracheal area diameter (p = 0.643) didn't show significance. Collagen type I, III, and Aggrecan highlighted no significant difference between the groups (both collagens with p = 0.445 and the Aggrecan p = 0.4). CONCLUSION: The scaffold appears to fit as a heterologous implant and did not trigger reactions such as rejection or extrusion of the material into the recipient. However, these results suggested that although the WJ matrix presents several characteristics as a biomaterial for tissue regeneration, it did not display histopathological benefits in trachea tissue regeneration.
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A perfect graft for wound care must be readily available without affecting the immune response, covering and protecting the wound bed. Considering previous studies have already established the use of hyaluronic acid (HA) for the treatment of wounds but the data presented on the amniotic membrane (AM) and its promising effects on healing still requires further investigation, this study aimed to evaluate the effects of the application of a decellularized amniotic membrane solubilized with hyaluronic acid on the healing process of cutaneous wounds on the 7th and 14th day, to evaluate the evolution of the wound and the inflammatory phases in these two times. Cutaneous lesions were excised from the dorsal region and 96 Wistar rats were divided into four groups: I-Excisional wound (EW); II-EW + AM; III-EW + HA; IV-EW + AM + HA. The present study demonstrated that the proposed combined therapy favors the tissue repair process of the epithelial lesion. Results showed a reduction in pro-inflammatory cytokines, an increase in anti-inflammatory cytokines, an increase in TGF-ß, and attenuation of oxidative stress, reducing the acute inflammatory response and promoting the beginning of tissue repair. We concluded that the proposed therapies accelerated the inflammatory process with anticipation of the repair phase.
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Amnios , Ácido Hialurónico , Ratas , Animales , Ácido Hialurónico/farmacología , Cicatrización de Heridas , Ratas Wistar , CitocinasRESUMEN
To investigate the effect of transplantation of stem cells from the bone marrow mononuclear cells (BMMC) associated with 15d-PGJ2-loaded nanoparticles in a rat model of chronic MI. Chronic myocardial infarction (MI) was induced by the ligation of the left anterior descending artery in 40 male Wistar rats. After surgery, we transplanted bone marrow associated with 15d-PGJ2-loaded nanoparticle by intramyocardial injection (106 cells/per injection) seven days post-MI. Myocardial infarction was confirmed by echocardiography, and histological analyses of infarct morphology, gap junctions, and angiogenesis were obtained. Our results from immunohistochemical analyses demonstrated the presence of angiogenesis identified in the transplanted region and that there was significant expression of connexin-43 gap junctions, showing a more effective electrical and mechanical integration of the host myocardium. This study suggests that the application of nanoparticle technology in the prevention and treatment of MI is an emerging field and can be a strategy for cardiac repair.
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OBJECTIVE: myocardial infarction (MI) remains the leading cause of death worldwide. Cell-based therapies have become potential therapeutic approaches, attempting to recover the contractility of necrotic cardiomyocytes. In the present study, we aimed to systematically evaluate experimental studies on the use of tissue-engineered amniotic membrane (hAMC) in MI treatment. METHODS: a systematic review of literature published in PubMed, Embase and CENTRAL databases was conducted, until March 31, 2020, for experimental studies reporting on hAMC cell-therapy performed on LV function, MI size, paracrine effects, angiogenesis, and cell differentiation. Two reviewers selected the articles that met the inclusion criteria and disagreements were solved through a consensus. RESULTS: a total of 11 studies were included for data extraction. For the acute scenario, therapeutic use of hAMC after MI was capable of improving LV function in rats, mainly due to its paracrine effects (anti-apoptotic and anti-inflammatory) and associated with cardiomyocyte differentiation, MI size reduction and neo-angiogenesis. CONCLUSION: tissue engineered hAMC following MI provided clinically relevant benefits on cardiac function and ventricular remodeling.
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OBJECTIVE: To compare and assess the immediate analgesic effects of conventional and burst transcutaneous electrical nerve stimulation in patients with chronic low back pain. METHODS: We conducted a three-arm single-blinded randomized controlled trial. A total of 105 patients with non-specific chronic low back pain aged between 18 and 85 years were randomly assigned into the following groups: Placebo Group (sham electrical stimulation), Conventional TENS Group (continuous stimulation at 100Hz for 100µs with sensory intensity), and Burst TENS Group (stimulation at 100Hz modulated at 2Hz for 100µs with motor-level intensity). All groups received a single application of transcutaneous electrical nerve stimulation for 30 minutes. The outcomes, namely, pain intensity, quality of pain, and pressure pain threshold were measured by the visual analog scale, McGill pain questionnaire, and algometry, respectively. The patients were evaluated before and immediately after the transcutaneous electrical nerve stimulation application. RESULTS: Pain intensity (visual analog scale score) and quality of pain (McGill pain questionnaire score) significantly decreased (p<0.05) in Intervention Groups (Conventional TENS Group and Burst TENS Group). A positive effect was observed in the interventions compared to the Placebo Group in all domains of the McGill pain questionnaire (p<0.05), excepting for the pain intensity. Pressure pain threshold significantly increased (p<0.05) immediately after the transcutaneous electrical nerve stimulation application in both Intervention Groups, but not in the Placebo Group. For significant difference was found during assessment when comparing both Intervetion Group. CONCLUSION: Both transcutaneous electrical nerve stimulation modes were effective for pain modulation. Moreover, there was an increase in the pressure pain threshold. No significant results were found to indicate the best mode for the treatment of chronic low back pain.Clinical Trial Registration: RBR-59YGRB.
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Dolor de la Región Lumbar , Estimulación Eléctrica Transcutánea del Nervio , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos/uso terapéutico , Humanos , Dolor de la Región Lumbar/terapia , Persona de Mediana Edad , Manejo del Dolor , Dimensión del Dolor , Resultado del Tratamiento , Adulto JovenRESUMEN
Myocardial infarction (MI) remains the leading cause of cardiovascular death worldwide and a major cause of heart failure. Recent studies have suggested that cell-based therapies with bone marrow stem cells (BMSC) and human amniotic membrane (hAM) would recover the ventricular function after MI; however, the mechanisms underlying these effects are still controversial. Herein, we aimed to compare the effects of BMSC and hAM in a rat model of heart failure. MI was induced through coronary occlusion, and animals with an ejection fraction (EF) < 50% were included and randomized into three groups: control, BMSC, and hAM. The BMSC and hAM groups were implanted on the anterior ventricular wall seven days after MI, and a new echocardiographic analysis was performed on the 30th day, followed by euthanasia. The echocardiographic results after 30 days showed significant improvements on EF and left-ventricular end-sistolic and end-diastolic volumes in both BMSC and hAM groups, without significant benefits in the control group. New blood vessels, desmine-positive cells and connexin-43 expression were also elevated in both BMSC and hAM groups. These results suggest a recovery of global cardiac function with the therapeutic use of both BMSC and hAM, associated with angiogenesis and cardiomyocyte regeneration after 30 days.
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Acellular amniotic membrane (AM) has been studied, with promising results on the reconstruction of lesioned tissues, and has become an attractive approach for tracheal repair. This study aimed to evaluate the repair of the trachea with human umbilical cord mesenchymal stem cells (hucMSCs) differentiated in chondrocytes, grown on an experimental model. Tracheal defects were induced by surgical tracheostomy in 30 New Zealand rabbits, and the acellular amniotic membrane, with or without cells, was covering the defect. The hucMSCs were isolated and cultivated with chondrogenic differentiation over the culture of 14 days, and then grown on the AM. In this study, the AM was biocompatible and hucMSCs differentiated into chondrocytes. Our results demonstrated an important role for AM with cultured cells in the promotion of immature collagen, known to produce tissue regeneration. In addition, cartilaginous tissue was found at the tracheal defects, demonstrated by immunohistology results. This study suggests that this biomaterial implantation can be an effective future therapeutic alternative for patients with tracheal injury.