Extracellular Vesicles as Delivery Systems in Disease Therapy.

Extracellular vesicles (EVs)/exosomes are nanosized membrane-bound structures that are released by virtually all cells. EVs have attracted great attention in the scientific community since the discovery of their roles in cell-to-cell communication. EVs' enclosed structure protects bioactive molecules from degradation in the extracellular space and targets specific tissues according to the topography of membrane proteins. Upon absorption by recipient cells, EV cargo can modify the transcription machinery and alter the cellular functions of these cells, playing a role in disease pathogenesis. EVs have been tested as the delivery system for the mRNA COVID-19 vaccine. Recently, different therapeutic strategies have been designed to use EVs as a delivery system for microRNAs and mRNA. In this review, we will focus on the exciting and various platforms related to using EVs as delivery vehicles, mainly in gene editing using CRISPR/Cas9, cancer therapy, drug delivery, and vaccines. We will also touch upon their roles in disease pathogenesis.

Bemiparin vs enoxaparin in the prevention of thrombosis in microvascular head and neck reconstruction.

This study aims to compare the use of Bemiparin vs Enoxaparin in patients undergoing microvascular head and neck reconstruction, analyzing the incidence of flap thrombotic complications and local bleeding that could compromise the flap survival. This is an observational study on a group of 204 patients who underwent a microvascular flap for head and neck reconstruction at the Oral and Maxillofacial Surgery Department of Ramon y Cajal Hospital in Madrid, Spain. A group of 67 patients was treated according to a protocol for postoperative prophylaxis of thromboembolism with Bemiparin, which was compared with data collected retrospectively from a group of 137 patients treated with Enoxaparin. We evaluated the incidence of thrombotic complications in the microvascular anastomoses and the incidence of postoperative bleeding events. The flap success rate was 91% in patients treated with Bemiparin, and 91,2% in the group of Enoxaparin (p = 0.963). One major bleeding event was recorded in the Bemiparin group, while 18 events were observed in the Enoxaparin group (p=0.008). Only the type of thromboprophylactic treatment (Bemiparin vs Enoxaparin) was related to presenting major bleeding (p = 0.007). Therefore, Bemiparin is useful in the thromboembolic prophylaxis in patients with microvascular head and neck reconstructions, providing a lower risk of major bleeding than Enoxaparin.

El colgajo submental en reconstrucción de defectos orofaciales / Submental flap in reconstruction of orofacial defects

Objetivo. Las técnicas microquirúrgicas con colgajos libres constituyen el «Gold Standard» en la reconstrucción inmediata de defectos postoncológicos de cabeza y cuello. Sin embargo, son procedimientos complejos, que requieren un alto grado de especialización, no exentos de complicaciones y morbilidad. El colgajo submental constituye una alternativa reconstructiva en el territorio maxilofacial, en casos en los que la reconstrucción microquirúrgica no está indicada. El objetivo del trabajo es mostrar los beneficios del empleo del colgajo submental en la reconstrucción maxilofacial. Material y método. Presentamos la experiencia recogida en el Servicio de Cirugía Oral y Maxilofacial del H.U. Ramón y Cajal de Madrid desde 2009 hasta 2013, registrando un total de 20 reconstrucciones realizadas con colgajo submental pediculado en pacientes con procesos neoplásicos a nivel intra y extraoral. Resultados. Los resultados fueron satisfactorios en 19 pacientes intervenidos, atendiendo a los criterios de cobertura del defecto, estética y funcionalidad. Se realizaron 12 disecciones cervicales funcionales electivas, con resultado histológico N0. En ningún caso se detectó transferencia de enfermedad tumoral cervical al lecho receptor. Solo se ha evidenciado recurrencia local de la enfermedad en un paciente. Conclusiones. El colgajo submental constituye una alternativa válida para la reconstrucción de defectos orofaciales, especialmente en aquellos pacientes que por edad o estado general deteriorado requieren tratamientos poco agresivos y con tiempos quirúrgicos reducidos. Requiere descartar la presencia de enfermedad metastásica ganglionar cervical previamente a su realización. Su empleo es controvertido para la reparación de defectos tras resección de tumores con alta linfofilia (AU)

Objective. The microsurgical techniques with free flaps are the 'Gold Standard' in the immediate reconstruction of post-cancer defects of the head and neck. However, procedures are complex, requiring a high degree of specialization, and not exempt from complications and morbidity. The submental flap is an alternative reconstruction technique in the maxillofacial field in cases where the microsurgical reconstruction is not indicated. The objective of this work is to show the benefits of the use of the submental flap in the maxillofacial reconstruction. Material and method. The experience of the Department of Oral and Maxillofacial Surgery of the H. U. Ramón y Cajal of Madrid from 2009 to 2013 is described, using the records of a total of 20 reconstructions made with submental pedicled flap in patients with intra- and extra-oral cancers. Results. The results were satisfactory in the 19 patients who underwent surgery, according to the criteria for coverage of the defect, aesthetics and functionality. There were 12 elective functional neck dissections, with histological findings, N0. In no case was transfer of cervical tumor disease to the recipient bed detected. There was only local recurrence of the disease in 1 patient. Conclusions. The submental flap constitutes a valid alternative for the reconstruction of orofacial defects, especially in elderly patients or patients that, due to deteriorated general condition require less aggressive treatments and reduced surgical times. Requires rule out The presence of cervical lymph node metastatic disease needs to be ruled out prior to surgery. Its use is controversial for the repair of defects after resection of tumors with high levels of tumor-infiltrating lymphocytes (AU)

¿Cuál sería su diagnóstico y tratamiento? / What would your diagnosis and treatment be?

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Angiofibroma nasofaríngeo juvenil: a propósito de un caso / Juvenile nasopharyngeal angiofibroma: presentation of a case

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Fibrodisplasia osificante progresiva. El papel del cirujano oral y maxilofacial. Experiencia en 2 casos / Fibrodysplasia ossificans progressiva. The role of oral and maxillofacial surgeon. experience in two cases

La fibrodisplasia osificante progresiva es un raro desorden genético que se caracteriza por la asociación de malformaciones congénitas y brotes de osificación heterotópica progresiva desde los primeros an˜ os de vida.El escaso número de pacientes que padecen la enfermedad, hace que el curso y tratamiento de la misma sea desconocida para muchos especialistas, pese a la importancia del manejo multidisciplinar de estos pacientes. Se presentan 2 casos valorados por nuestro servicio en los últimos 12 meses; 2 varones de 40 y 23 an˜ os diagnosticados de fibrodisplasia osificante progresiva en la infancia que acudieron a la consulta de cirugía maxilofacial para valoración y tratamiento (AU)

The ossificans progressive fibrodysplasia is a rare genetic disorder that is characterized by the association of congenital malformations and progressive heterotopic ossification outbreaks since the early years of life. The scanty number of patients who suffer the disease, does that the course and treatment of the same one is not known for many specialists, in spite of the importance of the multidisciplinary managing of these patients. We present 2 cases evaluated by our service in the last 12 months; two 40 and 23-year-old males diagnosed in childhood with ossificans progressive fibrodysplasia who attended the maxilofacial surgery department for evaluation and treatment (AU)

Purification and long-term expansion of multipotent endothelial-like cells with potential cardiovascular regeneration.

Endothelial progenitor cells (EPC) represent a relatively rare cell population, and expansion of sufficient cell numbers remains a challenge. Nevertheless, human adipose-derived stem cells (hASC) can be easily isolated and possess the ability to differentiate into endothelial cells. Here, we propose the isolation and characterization of multipotent endothelial-like cells (ME-LC) with the capacity to maintain their vascular progenitor properties for long periods. hASC were isolated from lipoaspirates and cultured through distinct consecutive culture stages for 2 months to enrich ME-LC: first in Dulbecco's modified Eagle's medium-fetal bovine serum (stage I), followed by a stage of culture in absent of fetal bovine serum (stage II), a culture in SFO3 medium (stage III), and, finally, the culture of ME-LC into collagen IV-coated flasks in endothelial growth medium (EGM-2) (stage IV). ME-LC display increased expression levels of endothelial and hematopoietic lineage markers (CD45, KDR, and CXCR4) and EPC markers (CD34 and CD133), whereas the expression of CD31 was barely detectable. Reverse transcription (RT)-polymerase chain reaction assays showed expression of genes involved in early stages of EPC differentiation and decreased expression of genes associated to differentiated EPC (TIE-2, DLL4, and FLT-1). ME-LC formed capillary-like structures when grown on Matrigel, secreted increased levels of stromal cell-derived factor-1 (SDF-1), and showed the ability to migrate attracted by SDF-1, vascular endothelial growth factor, and hematopoietic growth factor cytokines. Importantly, ME-LC retained the capacity to differentiate into cardiomyocyte-like cells. We present a simplified and efficient method to generate large numbers of autologous ME-LC from lipoaspirates-derived hASC, opening up potential cell-based therapies for cardiovascular regenerative medicine.

382 elevaciones de seno con técnica de ventana lateral y uso de biomaterial de relleno / Sinus augmentation with a lateral window technique and use of a biomaterial filling

Introducción. Desde los estudios de Boyne y James y Tatum, la elevación de seno maxilar y colocación de injertos óseos se ha convertido en un procedimiento estándar que permite la colocación de implantes dentales en casos en los que la altura ósea posterior del maxilar es insuficiente. Aunque la utilización de hueso autólogo se considera la técnica gold-standard, en la actualidad se utilizan diversos biomateriales que obvian los inconvenientes de los injertos autólogos. Uno de los biomateriales más ampliamente utilizados es la matriz mineral ósea bovina desproteinizada en forma de gránulos (Bio-Oss ®). Objetivos. Mostramos nuestra experiencia en implantología tras 382 elevaciones de seno. Material y métodos. Presentamos el estudio de una serie de 382 casos de elevaciones de seno maxilar realizadas con técnica abierta y abordaje lateral utilizando Bio-Oss® como material de relleno y colocando implantes dentales simultáneamente o en una fase posterior, describiendo los protocolos utilizados y el seguimiento. Resultados. Se realizaron un total de 382 casos (de los cuales 340 fueron en una sola fase y 42 en dos fases) durante el periodo comprendido entre octubre de 2002 y febrero de 2010. Se colocaron un total de 726 implantes de los cuales fracasaron 27 (3,7%). Conclusiones. La elevación de seno maxilar para colocación de implantes dentales utilizando Bio-Oss® como material de relleno es una técnica fiable y con resultados predecibles a largo plazo como pone de manifiesto nuestro estudio(AU)

Background. Since the studies of Boyne and James research and then Tatum, maxillary sinus floor augmentation and grafting has become a standard procedure for dental implants in cases where the bone height in posterior maxilla it was insufficient. Although autogenous graft is considered the gold standard, there is currently a large amount of biomaterials which avoid the problems of autogenous bone grafts. One of the most used biomaterials is deproteinised bovine bone mineral matrix in granules (Bio- Oss®). Objective. The purpose of this study is to report our experience after 382 sinus augmentations with a lateral window approach and Bio-Oss® graft. Material and Methods. The clinical records from 382 patients having posterior maxillary atrophy treated with lateral approach sinus floor augmentation, Bio-Oss® material graft and simultaneous or delayed dental implants. The technique used and short- term postoperative results were reviewed. Results. A total of 382 patients were treated (of which 340 were done in a single phase and 42 in two phases) during the period from October 2004 to January 2010. A total of 726 implants were made, of which 27 (3.7%) failed. Conclusions. Our study shows that maxillary sinus augmentation with Bio-Oss® and lateral window approach seems to be a reliable technique with predictable long-term results(AU)

Promotion of human adipose-derived stem cell proliferation mediated by exogenous nucleosides.

Adult stem cells are becoming the best option for regenerative medicine because they have low tumourigenic potential and permit autologous transplantation, even without in vitro culture. Our objectives were to evaluate the effects of exogenous nucleosides on the proliferation of hASCs (human adipose-derived stem cells), with or without co-treatment with 5-aza (5-azacytidine), and to analyse the expression of lamin A/C during cardiomyocyte differentiation of these cells. We isolated hASCs from human lipoaspirates that were positive for mesenchymal stem cell markers. We found that 5-aza induces a dose-dependent inhibition of hASC proliferation [IC50 (inhibitory concentration 50): 5.37 microM], whereas exogenous nucleosides significantly promote the proliferation of hASCs and partially revert the antiproliferative effect of the drug. Multipotentiality of isolated hASCs was confirmed by adipogenic, osteogenic and cardiomyogenic induction. 5-Aza-induced cells expressed cardiac troponins I and T and myosin light chain 2, myocardial markers that were directly correlated with lamin A/C expression. Our results support the importance of the nucleoside supplementation of media to improve conditions for the expansion and maintenance of hASCs in culture. In addition, the quantification of lamin A/C expression appears to be a good marker for the characterization of cardiomyocyte differentiation of stem cells that has rarely been used.