Loss of TJP1 disrupts gastrulation patterning and increases differentiation toward the germ cell lineage in human pluripotent stem cells.

Biological patterning events that occur early in development establish proper tissue morphogenesis. Identifying the mechanisms that guide these patterning events is necessary in order to understand the molecular drivers of development and disease and to build tissues in vitro. In this study, we use an in vitro model of gastrulation to study the role of tight junctions and apical/basolateral polarity in modulating bone morphogenic protein-4 (BMP4) signaling and gastrulation-associated patterning in colonies of human pluripotent stem cells (hPSCs). Disrupting tight junctions via knockdown (KD) of the scaffolding tight junction protein-1 (TJP1, also known as ZO1) allows BMP4 to robustly and ubiquitously activate pSMAD1/5 signaling over time, resulting in loss of the patterning phenotype and marked differentiation bias of pluripotent stem cells to primordial germ cell-like cells (PGCLCs). These findings give important insights into how signaling events are regulated and lead to spatial emergence of diverse cell types in vitro.

Marcadores moleculares y biomarcadores de imagen: importancia en el avance terapéutico de los tumores cerebrales intraaxiales / Molecular markers and image biomarkers. Importance in the therapeutic advance of intraaxial brain tumors

RESUMEN: La clasificación de los Tumores Primarios del Sistema Nervioso Central (SNC) tiene su origen en la descripción morfológica, cuyo análisis histopatológico ha permitido identificar la línea celular involucrada en estos tumores y obtener el reconocimiento de ciertas características de estas lesiones y su evolución clínica. El estudio molecular ha venido a complementar el diagnóstico inicial permitiendo reconocer entidades que no son distinguibles de otra manera y que han variado los conceptos y definiciones de varias entidades patológicas que modifican el horizonte visible de estas enfermedades. El papel de las imágenes de Resonancia Magnética (RM) en el manejo de los tumores intraaxiales se puede dividir ampliamente en el diagnóstico y la clasificación de los tumores, la planificación del tratamiento y el tratamiento posterior. El presente artículo resume la evidencia epidemiológica relacionada en la clasificación de los tumores primarios del SNC con marcadores moleculares y biomarcadores de imágenes de RM, apuntando a la importancia del uso de la investigación clínica con el manejo terapéutico.

SUMMARY: The classification of primary tumors of the Central Nervous System (CNS) has its origin in the morphological description whose histopathological analysis has allowed to identify the cell line involved in these tumors and obtain the recognition of certain characteristics of these lesions and their clinical evolution. The molecular study has come to complement the initial diagnosis allowing to recognize entities that are not distinguishable in another way and that have varied the concepts and definitions of various pathological entities modifying the visible horizon of these diseases. The role of Magnetic Resonance (MR) images in the management of intraaxial tumors can be broadly divided into the diagnosis and classification of tumors, treatment planning and subsequent treatment. The present article summarizes the epidemiologic evidence related to the classification of primary tumors of the CNS with molecular markers and MR imaging biomarkers.

Enhanced In Vivo Delivery of Stem Cells using Microporous Annealed Particle Scaffolds.

Delivery to the proper tissue compartment is a major obstacle hampering the potential of cellular therapeutics for medical conditions. Delivery of cells within biomaterials may improve localization, but traditional and newer void-forming hydrogels must be made in advance with cells being added into the scaffold during the manufacturing process. Injectable, in situ cross-linking microporous scaffolds are recently developed that demonstrate a remarkable ability to provide a matrix for cellular proliferation and growth in vitro in three dimensions. The ability of these scaffolds to deliver cells in vivo is currently unknown. Herein, it is shown that mesenchymal stem cells (MSCs) can be co-injected locally with microparticle scaffolds assembled in situ immediately following injection. MSC delivery within a microporous scaffold enhances MSC retention subcutaneously when compared to cell delivery alone or delivery within traditional in situ cross-linked nanoporous hydrogels. After two weeks, endothelial cells forming blood vessels are recruited to the scaffold and cells retaining the MSC marker CD29 remain viable within the scaffold. These findings highlight the utility of this approach in achieving localized delivery of stem cells through an injectable porous matrix while limiting obstacles of introducing cells within the scaffold manufacturing process.

[Vestibular schwannomas: Surgical treatment of 67 cases in 10 years]. / Schwannomas vestibulares: experiencia en el tratamiento quirúrgico de 67 casos en 10 años.

INTRODUCTION: Vestibular Schwannomas (VS) are benign intracranial tumors, for which their current management is a matter of debate, although microsurgical treatment remains the mode of choice in the majority of cases. OBJECTIVE: To describe the surgical outcome of patients operated on for a VS in a Chilean Public Hospital. MATERIAL AND METHOD: A series of 67 patients treated surgically between 2002 and 2012, in the Institute of Neurosurgery Asenjo is presented. RESULTS: Sixty-five cases (97%) corresponded to Koos III and IV tumors, of which 52% were large (3-4 cm) or Giant (>4 cm). Forty-one cases were operated on using a retrosigmoid transmeatalapproach (61%). Total resection was achieved in 97% of the cases and subtotal in the remaining 3%. A mean six months follow-up showed that good facial function (House-Brackmann I or II) was obtained in 32.7% of the patients, and moderate function (House-Brackmann III or IV) in 42.3%. Cardiopulmonary complications were the most frequent (28%), and mortality was 1.5%. CONCLUSIONS: The VS are tumors that can cause significant neurological deficit in advanced stages, despite their benign nature. Surgical treatment is very complex, and must be performed by specialized teams to ensure optimal functional results.

Manejo multidisciplinario de la acromegalia / Multidisciplinary management of acromegaly

Acromegaly is a chronic disease caused in most cases by hypophysiary adenoma. It is of complex management due to the high variability of the causing lesion and its clinical repercussion. Surgical outcomes are poor with remission rates of 80 percent for microadenomas and 50 percent for macroadenomas. The author's experience in treating 38 patients with this pathology as well as the remission results of the illness and the complications are presented herein. Handling alternatives and associated complications are discussed and a clinical case is presented to show the therapeutical options in more complex cases.

La acromegalia es una enfermedad crónica causada en la mayoría de los casos por un adenoma hipofisario. Su manejo es complejo por la gran variabilidad de la lesión causante y su repercusión clínica. Los resultados quirúrgicos son pobres, con tasas de remisión de la enfermedad en promedio de un 80 por ciento en microadenomas y 50 por ciento en macroadenomas. Se presenta la experiencia del autor en el manejo de esta patología en 38 pacientes, los resultados de remisión de la enfermedad. Se discute las alternativas de manejo, complicaciones asociadas y se ilustra con un caso clínico para demostrar las opciones terapéuticas en los casos más complejos.

Revascularization for complex skull base tumors.

We discuss revascularization techniques for complex skull base lesions utilizing high-flow arterial bypass. At present, the radial artery is the donor graft utilized in most circumstances at our institution. The knowledge of revascularization techniques is very important to achieve radical resection in lesions where arterial compromise is documented.

Manejo neuroquirúrgico de los cavernomas del sistema nervioso central / Neurosurgical treatment of central nervous system cavernous angiomas

Los cavernomas o angiomas cavernosos son malformaciones hamartomatosas vasculares benignas, en su mayoría encefálicas y supratentoriales, con prevalencia descrita entre el 0,1 y el 4 por ciento de la población general, de presentación esporádica o familiar. El presente estudio analiza los aspectos epidemiológicos, clínicos y pronósticos de los casos tratados en el Instituto de Neurocirugía Asenjo durante el año 2000. Para ello se recopiló información de 13 casos operados desde las fichas médicas y de los protocolos operatorios, registrándolos en una matriz Excel® para su análisis. Los resultados permiten concluir que el cuadro clínico de presentación es de tipo comicial en la mayoría de los pacientes de nuestra serie. La cirugía se plantea sólo en los casos sintomáticos. En nuestro centro las cifras de morbimortalidad son similares a las presentadas en la literatura internacional. Las lesiones profundas son un desafío por la dificultad técnica de los accesos y porque están asociadas a mayores complicaciones.