ABSTRACT
Skeletal muscle plays a paramount role in physical activity, metabolism, and energy balance, while its homeostasis is being challenged by multiple unfavorable factors such as injury, aging, or obesity. Exosomes, a subset of extracellular vesicles, are now recognized as essential mediators of intercellular communication, holding great clinical potential in the treatment of skeletal muscle diseases. Herein, we outline the recent research progress in exosomal isolation, characterization, and mechanism of action, and emphatically discuss current advances in exosomes derived from multiple organs and tissues, and engineered exosomes regarding the regulation of physiological and pathological development of skeletal muscle. These remarkable advances expand our understanding of myogenesis and muscle diseases. Meanwhile, the engineered exosome, as an endogenous nanocarrier combined with advanced design methodologies of biomolecules, will help to open up innovative therapeutic perspectives for the treatment of muscle diseases.
Subject(s)
Exosomes/physiology , Muscle, Skeletal/metabolism , Cell Communication , HomeostasisABSTRACT
The study aims to explore the effect of mesenchymal stem cells-derived exosomes (MSCs-Exo) on staurosporine (STS)-induced chondrocyte apoptosis before and after exposure to pulsed electromagnetic field (PEMF) at different frequencies. The AMSCs were extracted from the epididymal fat of healthy rats before and after exposure to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. MSCs-Exo was extracted and identified. Exosomes were labeled with DiO fluorescent dye, and then co-cultured with STS-induced chondrocytes for 24 h. Cellular uptake of MSC-Exo, apoptosis, and the protein and mRNA expression of aggrecan, caspase-3 and collagenⅡA in chondrocytes were observed. The study demonstrated that the exposure of 75 Hz PEMF was superior to 15 and 45 Hz PEMF in enhancing the effect of exosomes in alleviating chondrocyte apoptosis and promoting cell matrix synthesis. This study lays a foundation for the regulatory mechanism of PEMF stimulation on MSCs-Exo in inhibiting chondrocyte apoptosis, and opens up a new direction for the prevention and treatment of osteoarthritis.
Subject(s)
Animals , Rats , Apoptosis , Chondrocytes , Electromagnetic Fields , Exosomes/physiology , Mesenchymal Stem Cells/metabolismABSTRACT
Exosomes are a class of extracellular vesicles with a structure of lipid bilayer-membrane. In the central nervous system (CNS), exosomes can be secreted from both neurons and glial cells. Exosomes released into the extracellular matrix can freely cross the blood-brain barrier and function as crucial carriers of cellular communication and substance exchange in the CNS. Exosomes play a key role in the pathological process of mental disorders such as schizophrenia, depression, and bipolar disorder, and they have the potential to be used as a targeted carrier of antipsychotic medications. Exosomes are likely to become a new tool in the future to aid in the early prevention, accurate diagnosis, and effective treatment for people with mental disorders.
Subject(s)
Humans , Exosomes/physiology , Extracellular Vesicles/physiology , Central Nervous System , Mental Disorders , Blood-Brain BarrierABSTRACT
Resumen Los exosomas tienen un papel clave en la comunicación intercelular. Debido a sus múltiples interacciones, estas estructuras cumplen con el papel de «mensajeros¼ de forma dinámica, transportando su contenido a células blanco específicas y generando nuevas señales celulares. En este artículo se describen algunas de las proteínas, lípidos y ácidos nucleicos que son transportados por estas vesículas y que se han relacionado con cardioprotección, con la finalidad de proporcionar información y generar interés sobre la relevancia de los exosomas como posibles blancos diagnósticos y terapéuticos.
Abstract Exosomes have a key role in intercellular communication. Due to their multiple interactions, these structures fulfill the role of messengers in a dynamic way, transporting their content to target-specific cells and generating new cellular signals. This article describes some of the proteins, lipids and nucleic acids that are transported by these vesicles and that have been related to cardioprotection, in order to provide information and generate interest in the relevance of exosomes as possible diagnostic and therapeutic targets.
Subject(s)
Humans , Exosomes/physiology , Heart/physiologyABSTRACT
La terapia celular basada en células mesenquimales/estromales se aplica ampliamente en la medicina moderna, aun cuando no todos los mecanismos de supervivencia y diferenciación están identificados. Sin embargo, hace pocos años se comenzaron a encontrar elementos extracelulares que generan nuevos paradigmas. En el presente trabajo se explican las principales características y funciones atribuidas a los exosomas, nanopartículas constituidas por microvesículas secretadas por las células con efecto en la matriz extracelular, y su repercusión como alternativa hacia una medicina regenerativa libre de células. Estas estructuras participan de forma notoria y crucial en la comunicación intercelular, lo que ha supuesto un cambio en el concepto de las funciones y el papel que desempeñan estas vesículas en los organismos vivos, en particular en la restauración de tejidos dañados y la respuesta inflamatoria e inmunológica. Se comentan algunos ejemplos de la repercusión biotecnológica de los exosomas en empresas y el mercado biofarmaceútico(AU)
Mesenchymal/stromal cell ;based therapy is widely applied in modern medicine, even though not all survival and differentiation mechanisms are identified. However, a few years ago, extracellular elements began to be found that generate new paradigms. The present work explains the main characteristics and functions attributed to exosomes, nanoparticles made up of microvesicles secreted by with an effect on the extracellular matrix, and their impact as an alternative towards cell-free regenerative medicine. These structures participate, notoriously and critically, in intercellular communication, which has led to a change in the concept of the functions and role that these vesicles play within living organisms, particularly in the restoration of damaged tissues and the inflammatory and immunological response. Some examples of the exosomes' biotechnological impact on companies and the biopharmaceutical market are discussed(AU)
Subject(s)
Humans , Male , Female , Regenerative Medicine/methods , Exosomes/physiology , Mesenchymal Stem Cells/physiologyABSTRACT
Introducción: La Troponina I (TnI) plasmática es el biomarcador "Gold" estándar utilizado en diagnóstico de Infarto Agudo al Miocardio (IAM), indicando necrosis cardíaca. Las microvesículas extracelulares (MVEC), participan en comunicación celular, por lo que estudiar su distribución entregaría información respecto del evento isquémico, antesala del infarto. Objetivo: Estudiar las MVECs plasmáticas en pacientes con Síndrome Coronario Agudo (SCA) y compararlas con los niveles de TnI. Métodos: Plasma de 22 pacientes controles se recolectó 0-2hrs post-ingreso a urgencia. Plasma de 45 pacientes SCA se recolectó 0-2, 6-8 y 10-14hrs post ingreso, junto con la toma de muestra para estudio de TnI. Las MVECs plasmáticas fueron enriquecidas mediante kit comercial. La determinación de la concentración y tamaño MVECs se realizó por NTA (Nanoparticles Tracking Assay) usando el equipo Nanosight. Resultados: La concentración promedio de MVECs 0-2 hrs post ingreso fue 7,2 veces superior en plasma de pacientes con SCA vs controles y la moda del tamaño disminuyó en pacientes con SCA. La TnI no mostró diferencias significativas en 0-2 hrs post ingreso en el grupo estudiado. La concentración de las MVEC disminuyó significativamente después de 10-14 hrs post ingreso, mientras que la concentración promedio TnI se mantuvo invariable demostrando el aumento de MVECs previo al incremento de TnI. Conclusión. El aumento de MVECs previo al incremento de la TnI en pacientes infartados, sugiere que las MVECs aumentan en la fase previa del IAM, como respuesta al daño tisular. Actualmente, estudiamos el contenido molecular de las MVECs, para establecer un método diagnóstico del Síndrome Coronario Agudo basado en MVECs.
Background: Troponin I (TnI) is the gold standard used to establish the diagnosis of myocardial infarction (AMI), indicating the presence of myocardial necrosis. Extracellular micro vesicles are involved in cellular communication. Their distribution may provide information relating to the development of AMI in patients with acute coronary syndromes (ACS) Aim: to study plasma levels of ECMV compared to those of TnI in patients with ACS. Methods: The plasma levels of TnI and ECMV from 22 control patients coming to the emergency units was compared to plasma from 45 patients with ACS. Levels of both parameters were determined 0-2, 6-8 and 10-14 hours post admission. ECMVs were enriched by means of a commercial kit. Concentration and size of ECMV was determined by NTA (Nanoparticles tracking assay) using the Nanosight equipment. Results: Plasma concentration of ECMV was 7.2 times higher than that of TnI 0-2 hrs post admission. The mode of ECMV size was lower in patients with ACS. Concentration of ECMV had decreased significantly 10-14 hrs post admission, whereas the TnI levees remained stable. Conclusion: The increase in ECMV earlier than TnI in AMI suggests that ECMV are elevated in the pre-AMI phase, as a response to early tissue damage. A study of cellular content of ECMV, being carried out, may lead to develop a method for the early diagnosis of AMI in patients with ACS.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Extracellular Vesicles/physiology , Myocardial Infarction/blood , Myocardial Infarction/metabolism , Troponin I/blood , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/metabolism , Analysis of Variance , Biomarkers/blood , Cell Tracking/methods , Exosomes/physiology , NanoparticlesABSTRACT
AbstractPulmonary hypertension is a devastating and refractory disease and there is no cure for this disease. Recently, microRNAs and mesenchymal stem cells emerged as novel methods to treat pulmonary hypertension. More than 20 kinds of microRNAs may participate in the process of pulmonary hypertension. It seems microRNAs or mesenchymal stem cells can ameliorate some symptoms of pulmonary hypertension in animals and even improve heart and lung function during pulmonary hypertension. Nevertheless, the relationship between mesenchymal stem cells, microRNAs and pulmonary hypertension is not clear. And the mechanisms underlying their function still need to be investigated. In this study we review the recent findings in mesenchymal stem cells - and microRNAs-based pulmonary hypertension treatment, focusing on the potential role of microRNAs regulated mesenchymal stem cells in pulmonary hypertension and the role of exosomes between mesenchymal stem cells and pulmonary hypertension.
ResumoA hipertensão pulmonar é uma doença devastadora e refratária, para a qual não existe cura. Recentemente, microRNAs e células-tronco mesenquimais emergiram como novos métodos para tratar a hipertensão pulmonar. Mais de 20 tipos de microRNAs podem participar no processo de hipertensão pulmonar. Ao que parece, microRNAs ou células-tronco mesenquimais podem atenuar alguns sintomas de hipertensão pulmonar em animais de e até mesmo melhorar a função cardíaca e do pulmão durante a hipertensão pulmonar. No entanto, a relação entre células-tronco mesenquimais, microRNAs e hipertensão pulmonar não é clara. E os mecanismos subjacentes a sua função ainda precisam ser investigados. Neste estudo, revisamos as descobertas recentes no tratamento da hipertensão pulmonar baseado em células-tronco mesenquimais e microRNAs, enfocando o papel potencial dos microRNAs para regular as células-tronco mesenquimais na hipertensão pulmonar e o papel dos exossomos entre células-tronco mesenquimais e hipertensão pulmonar.
Subject(s)
Animals , Humans , Hypertension, Pulmonary/therapy , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/physiology , MicroRNAs/therapeutic use , Exosomes/physiology , Hypertension, Pulmonary/physiopathology , Lung/physiopathologyABSTRACT
Interest in the role of extracellular vesicles in various diseases including cancer has been increasing. Extracellular vesicles include microvesicles, exosomes, apoptotic bodies, and argosomes, and are classified by size, content, synthesis, and function. Currently, the best characterized are exosomes and microvesicles. Exosomes are small vesicles (40-100 nm) involved in intercellular communication regardless of the distance between them. They are found in various biological fluids such as plasma, serum, and breast milk, and are formed from multivesicular bodies through the inward budding of the endosome membrane. Microvesicles are 100-1000 nm vesicles released from the cell by the outward budding of the plasma membrane. The therapeutic potential of extracellular vesicles is very broad, with applications including a route of drug delivery and as biomarkers for diagnosis. Extracellular vesicles extracted from stem cells may be used for treatment of many diseases including kidney diseases. This review highlights mechanisms of synthesis and function, and the potential uses of well-characterized extracellular vesicles, mainly exosomes, with a special focus on renal functions and diseases.
Subject(s)
Humans , Cell Communication/physiology , Cell Membrane/physiology , Exosomes/physiology , Kidney Diseases , Kidney Diseases/diagnosis , Kidney Diseases/physiopathology , Kidney Diseases/therapyABSTRACT
In addition to the established mechanisms of intercellular signaling, a new way of communication has gained much attention in the last decade: communication mediated by exosomes. Exosomes are nanovesicles (with a diameter of 40-120 nm) secreted into the extracellular space by the multivesicular endosome after its outer membrane fuses with the plasma membrane. Once released, exosomes modulate the response of the recipient cells that recognize them. This indicates that exosomes operate in a specific manner and participate in the regulation of the target cell. Remarkably, exosomes occur from unicellular organisms to mammals, suggesting an evolutionarily conserved mechanism of communication. In this review we describe the cascade of exosome formation, intracellular traffic, secretion, and internalization by recipient cells, and review their most relevant effects. We also highlight important steps that are still poorly understood.