Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity.

Cell transplantation therapies in the nervous system are frequently hampered by glial scarring and cell drain from the damaged site, among others. To improve this situation, new biomaterials may be of help. Here, novel single-channel tubular conduits based on hyaluronic acid (HA) with and without poly-l-lactide acid fibers in their lumen were fabricated. Rat Schwann cells were seeded within the conduits and cultured for 10days. The conduits possessed a three-layered porous structure that impeded the leakage of the cells seeded in their interior and made them impervious to cell invasion from the exterior, while allowing free transport of nutrients and other molecules needed for cell survival. The channel's surface acted as a template for the formation of a cylindrical sheath-like tapestry of Schwann cells continuously spanning the whole length of the lumen. Schwann-cell tubes having a diameter of around 0.5mm and variable lengths can thus be generated. This structure is not found in nature and represents a truly engineered tissue, the outcome of the specific cell-material interactions. The conduits might be useful to sustain and protect cells for transplantation, and the biohybrids here described, together with neuronal precursors, might be of help in building bridges across significant distances in the central and peripheral nervous system. STATEMENT OF SIGNIFICANCE: The paper entitled "Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity" reports on the development of a novel tubular scaffold and on how this scaffold acts on Schwann cells seeded in its interior as a template to produce macroscopic hollow continuous cylinders of tightly joined Schwann cells. This cellular structure is not found in nature and represents a truly engineered novel tissue, which obtains as a consequence of the specific cell-material interactions within the scaffold.

[Brain neuroplasticity in occipital areas in blind teenagers]. / Neuroplasticidad cerebral en áreas occipitales en adolescentes ciegos.

INTRODUCTION AND DEVELOPMENT: Neuroplasticity is a process by which neurons increase their connectivity with other neurons in a stable fashion as a consequence of experience, learning and both sensitive and cognitive stimulation. Different authors have shown a huge process of brain plasticity in blind subjects towards other sensorial areas, mainly auditive and visual ones. From an anatomical standpoint many data show significant differences in blind subjects brains, mainly in visual pathways and structures as a result of lack of activity on those areas. This brings a lesser neuroplasticity and, therefore, a decrease in structural volumes. They have also found differences in subcortical structures volumes related to vision, such as splenium or corpus callosum istmus. METHODOLOGY: An adolescent was administered passive tactile stimulation with an 1,500 taxels stimulator. This was carried out daily for an hour, for three months, and stimulation consisted of vertical, horizontal and oblique lines. The results obtained in an adolescent indicate a clear progression of EEG activity from tactile sensory parietal areas to visual occipital ones as stimulation progresses. CONCLUSION: Therefore one can speculate if systematic and organized repetition of tactile stimuli in blind subjects leads to a greater neuroplasticity which expands towards occipital areas, largely responsible for human vision.

[Experimental models of cerebral ischemia]. / Modelos experimentales de isquemia cerebral.

AIM: To provide a summary of the different experimental models of cerebral ischemia designed both under in vivo and in vitro conditions. A clear and concise description of the specific types of brain lesion reproduced by each model is given together with the most frequent technical troubles associated. DEVELOPMENT: Experimental models of cerebral ischemia have contributed substantially to the understanding of the physiopathology of the ischemic brain injury and to test the beneficial effects of new therapies. Outcome of patients suffering from an ischemic stroke has improved considerably with the use of these models, particularly after the introduction of thrombolytic and neuroprotective drugs. Experimental models allow the study of the evolving ischemic brain injury under strict and controlled conditions. Usefulness of experimental models is limited by their reliability, simplicity and reproducibility among different researchers. Small rodents, especially rats, have been the preferred animals used to develop models of cerebral ischemic injury, due to their cerebral physiology and vascularisation which is closer to the human. CONCLUSION: The use of experimental models of cerebral ischemia constitutes the most suitable tool to investigate the physiopathology of this type of injury. However their simplicity prevents an exact reproduction of the cerebral damage observed in clinical settings. This could be the main reason for the discrepancies observed between the therapeutic effect in the experimental and clinical studies.

[Experimental models of Huntington's disease]. / Modelos experimentales de la enfermedad de Huntington.

INTRODUCTION: Huntington's disease (HD) is an autosomal dominant hereditary disease caused by triplet repetition in exon 1 of the huntingtin protein located in chromosome 4. Medium spiny neurons in the striatum are selectively affected. Clinical manifestations include progressive behavioural, motor and cognitive disorders. There is no treatment available today capable of modifying the natural course of the disease. A great amount of research work is being carried out, much of which involves animal models of the disease. DEVELOPMENT: We reviewed the articles published in PubMed on basic research into HD and analysed the most frequently used models. Transgenic mouse models, excitotoxic models, transgenic fly models and cell cultures are all used in studies into HD. The advantages and disadvantages of each of them are highlighted. CONCLUSION: The contribution made by each model of HD must be known in order to draw up a correct design in experimental studies of the disease.

Síndrome de piernas inquietas grave tras estimulación subtalámica bilateral para tratar una paciente con enfermedad de Parkinson / Severe restless legs syndrome following bilateral subthalamic

No disponible

No disponible

[Regenerative medicine with adult stem cells]. / Medicina regenerativa con células madre adultas.

The present state of clinical regenerative medicine with adult stem cells in the cardiology, digestive, corneal and neurological fields are reviewed. From the cardiology point of view, there is clinical experience with bone marrow stem cells and peripheral blood cells and with skeletal myoblasts. At present, the adult stem cells (bone marrow hematopoietic or mesenchymal) constitute the best option for the regeneration of heart tissue, the clinical studies showing favorable results without ethical or safety problems. Most of the studies with skeletal myoblasts have also been demonstrated to significantly contribute to improve heart function, above all, the systolic one. However they have the disadvantage that has not been totally clarified that they induce malignant ventricular arrhythmias. In either case, the clinical studies are in the initial phase and new studies, above all randomized, are necessary. In the digestive field, there is the pioneer experience of the Hospital La Paz on the use of stem cells from abdominal fat in the treatment of fistulous condition of patients with Crohn's disease. In ophthalmology, the limbal corneal transplant is a recognized practice, using cells from the contralateral eye when the damage is in a single eye and cells from a donor when the damage is bilateral. Finally, in the neurological field, different zones of the adult mammal brain where there are stem cells have been identified: the hippocampus, subventricular zone, olfactory bulb and periependymal zone of the spinal cord. On the other hand, neurons may be obtained from adult stem cells from other tissues, such as the bone marrow or adipose tissue, which means a practically unendable source of neural precursors, either by direct implant after their selection or after their in vitro culture. However, most of the experimentation is animal up to now, clinical trails on safety in amyotrophic lateral sclerosis are now being initiated.

Medicina regenerativa con células madre adultas / Regenerative medicine with adult stem cells

En este trabajo se revisa el estado actual de la medicina regenerativa clínica con células madre de adulto en los campos cardiológico, digestivo, corneal y neurológico. Desde el punto de vista cardiológico existe experiencia clínica con progenitores de médula ósea y células de sangre periférica, así como con mioblastos esqueléticos. En el momento actual las células madre del adulto (hematopoyéticas o mesenquimales de médula ósea) constituyen la mejor opción para la regeneración del tejido cardíaco, mostrando los estudios clínicos resultados favorables, sin problemas éticos ni de seguridad. La mayoría de los estudios con mioblastos esqueléticos también han demostrado que contribuyen significativamente a mejorar la función cardíaca, sobre todo la sistólica, aunque tienen el inconveniente no aclarado totalmente, de inducir arritmias ventriculares malignas. Tanto en uno como en otro caso los estudios clínicos están en la fase inicial y se hace necesario nuevos estudios sobre todo randomizados. En el campo digestivo se presenta la experiencia pionera del Hospital La Paz del uso de células madre procedentes de la grasa abdominal en el tratamiento de la patología fistulosa de pacientes con enfermedad de Crohn. En Oftalmología el trasplante de limbo corneal es una práctica reconocida, usándose células del ojo contralateral cuando el daño es en un solo ojo y células de un donante cuando el daño es bilateral. Por último, en el campo neurológico se han identificado diversas zonas del cerebro de mamíferos adultos donde existen células troncales: el hipocampo, la zona subventricular, el bulbo olfatorio y la zona periependimaria de la médula espinal. Por otra parte, es posible obtener neuronas a partir de células troncales adultas procedentes de otros tejidos, como la médula ósea o el tejido adiposo, lo que supondría una fuente prácticamente inagotable de precursores neurales, bien mediante implante directo tras su selección o bien tras su cultivo in vitro. Aunque hasta la fecha la mayor parte de la experimentación es animal, se están poniendo ya en marcha ensayos clínicos de seguridad en esclerosis lateral amiotrófica

The present state of clinical regenerative medicine with adult stem cells in the cardiology, digestive, corneal and neurological fields are reviewed. From the cardiology point of view, there is clinical experience with bone marrow stem cells and peripheral blood cells and with skeletal myoblasts. At present, the adult stem cells (bone marrow hematopoietics or mesenchymal) constitute the best option for the regeneration of heart tissue, the clinical studies showing favorable results without ethical or safety problems. Most of the studies with skeletal myoblasts have also been demonstrated to significantly contribute to improve heart function, above all, the systolic one. However they have the disadvantage that has not been totally clarified that they induce malignant ventricular arrhythmias. In either case, the clinical studies are in the initial phase and new studies, above all randomized, are necessary. In the digestive field, there is the pioneer experience of the Hospital La Paz on the use of stem cells from abdominal fat in the treatment of fistulous condition of patients with Chron disease. In ophthalmology, the limbal corneal transplant is a recognized practice, using cells from the contralateral eye when the damage is in a single eye and cells from a donor when the damage is bilateral. Finally, in the neurological field, different zones of the adult mammal brain where there are stem cells have been identified: the hippocampus, subventricular zone, olfactory bulb and periependymal zone of the spinal cord. On the other hand, neurons may be obtained from adult stem cells from other tissues, such as the bone marrow or adipose tissue, which means a practically unendable source of neural precursors, either by direct implant after their selection or after their in vitro culture. However, most of the experimentation is animal up to now, clinical trails on safety in amyotrophic lateral sclerosis are now being initiated

[Prognosis value of p53 gene and cellular proliferation factors in malignant supratentorial gliomas]. / Significación pronóstica de los factores de proliferación celular y del gen p53 en gliomas malignos supratentoriales del adulto.

OBJECT: The aim of this study was to investigate prognosis value of p53 oncosuppresor gene and labeling index by MIB-1 and PCNA monoclonal antibodies in malignant gliomas. METHODS AND RESULTS: We operated 60 patient with malignant glioma between July 1994 and August 1998. Forty-five cases had the histopathological diagnosis of Glioblastoma Multiforme and fifteen cases of anaplastic astrocytoma or olygoastrocytoma. Initially we compare MIB-1/PCNA labeling index in eighteen cases. Patients < 40 years old, short period of symptoms preoperatively, only one cerebral lobe localization, total surgical exeresis, Karnofsky index > 70 postoperatively, low labeling index (MIB < 8.6%), forward radiotherapy treatment and surgical re-operation, were identified like favourable outcome factors in the uninvariable analysis. However to the multivariable analysis, only had outcome significance: patients < 40 years old, low labeling index, Karnofsky index > 70 postoperatively and surgical reoperation. CONCLUSIONS: On the basis of the results of current analysis, moreover classical factors associated with better outcome, low labeling index to Glioblastoma Multiforme have been noted in patients with longer survival, and must be included to conventional histopathological studies.