Research Center Biomedica En Red Of Bioingenieria

Barcelona, Spain

Research Center Biomedica En Red Of Bioingenieria

Barcelona, Spain

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Navarro S.,CIEMAT | Navarro S.,CIBER ISCIII | Moleiro V.,CIEMAT | Moleiro V.,CIBER ISCIII | And 29 more authors.
Stem Cells | Year: 2014

Fanconi anemia (FA) is a complex genetic disease associated with a defective DNA repair pathway known as the FA pathway. In contrast to many other FA proteins, BRCA2 participates downstream in this pathway and has a critical role in homology-directed recombination (HDR). In our current studies, we have observed an extremely low reprogramming efficiency in cells with a hypomorphic mutation in Brca2 (Brca2Δ27/Δ27), that was associated with increased apoptosis and defective generation of nuclear RAD51 foci during the reprogramming process. Gene complementation facilitated the generation of Brca2Δ27/Δ27 induced pluripotent stem cells (iPSCs) with a disease-free FA phenotype. Karyotype analyses and comparative genome hybridization arrays of complemented Brca2Δ27/Δ27 iPSCs showed, however, the presence of different genetic alterations in these cells, most of which were not evident in their parental Brca2 Δ27/Δ27 mouse embryonic fibroblasts. Gene-corrected Brca2Δ27/Δ27 iPSCs could be differentiated in vitro toward the hematopoietic lineage, although with a more limited efficacy than WT iPSCs or mouse embryonic stem cells, and did not engraft in irradiated Brca2Δ27/Δ27 recipients. Our results are consistent with previous studies proposing that HDR is critical for cell reprogramming and demonstrate that reprogramming defects characteristic of Brca2 mutant cells can be efficiently overcome by gene complementation. Finally, based on analysis of the phenotype, genetic stability, and hematopoietic differentiation potential of gene-corrected Brca2Δ27/Δ27 iPSCs, achievements and limitations in the application of current reprogramming approaches in hematopoietic stem cell therapy are also discussed. © AlphaMed Press 2013.


Garde A.,Polytechnic University of Catalonia | Garde A.,Institute Of Bioenginyeria Of Catalonia | Garde A.,Research Center Biomedica En Red Of Bioingenieria | Sornmo L.,Lund University | And 6 more authors.
IEEE Transactions on Biomedical Engineering | Year: 2010

A correntropy-based technique is proposed for the characterization and classification of respiratory flow signals in chronic heart failure (CHF) patients with periodic or nonperiodic breathing (PB or nPB, respectively) and healthy subjects. The correntropy is a recently introduced, generalized correlation measure whose properties lend themselves to the definition of a correntropy-based spectral density (CSD). Using this technique, both respiratory and modulation frequencies can be reliably detected at their original positions in the spectrum without prior demodulation of the flow signal. Single-parameter classification of respiratory patterns is investigated for three different parameters extracted from the respiratory and modulation frequency bands of the CSD, and one parameter defined by the correntropy mean. The results show that the ratio between the powers in the modulation and respiratory frequency bands provides the best result when classifying CHF patients with either PB or nPB, yielding an accuracy of 88.9%. The correntropy mean offers excellent performance when classifying CHF patients versus healthy subjects, yielding an accuracy of 95.2% and discriminating nPB patients from healthy subjects with an accuracy of 94.4%. © 2010 IEEE.


Rigat-Brugarolas L.G.,Institute for Bioengineering of Catalonia IBEC | Rigat-Brugarolas L.G.,Research Center Biomedica En Red Of Bioingenieria | Elizalde-Torrent A.,University of Barcelona | Bernabeu M.,University of Barcelona | And 10 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2014

The spleen is a secondary lymphoid organ specialized in the filtration of senescent, damaged, or infected red blood cells. This unique filtering capacity is largely due to blood microcirculation through filtration beds of the splenic red pulp in an open-slow microcirculation compartment where the hematocrit increases, facilitating the recognition and destruction of unhealthy red blood cells by specialized macrophages. Moreover, in sinusal spleens such as those of humans, blood in the open-slow microcirculation compartment has a unidirectional passage through interendothelial slits before reaching the venous system. This further physical constraint represents a second stringent test for erythrocytes ensuring elimination of those cells lacking deformability. With the aim of replicating the filtering function of the spleen on a chip, we have designed a novel microengineered device mimicking the hydrodynamic forces and the physical properties of the splenon, the minimal functional unit of the red pulp able to maintain filtering functions. In this biomimetic platform, we have evaluated the mechanical and physiological responses of the splenon using human red blood cells and malaria-infected cells. This novel device should facilitate future functional studies of the spleen in relation to malaria and other hematological disorders. © 2014 the Partner Organisations.


Villegas M.R.,Complutense University of Madrid | Villegas M.R.,Research Center Biomedica En Red Of Bioingenieria | Baeza A.,Complutense University of Madrid | Baeza A.,Research Center Biomedica En Red Of Bioingenieria | And 2 more authors.
ACS Applied Materials and Interfaces | Year: 2015

Poor penetration of drug delivery nanocarriers within dense extracellular matrices constitutes one of the main liabilities of current nanomedicines. The conjugation of proteolytic enzymes on the nanoparticle surface constitutes an attractive alternative. However, the scarce resistance of these enzymes against the action of proteases or other aggressive agents present in the bloodstream strongly limits their application. Herein, a novel nanodevice able to transport proteolytic enzymes coated with an engineered pH-responsive polymeric is presented. This degradable coat protects the housed enzymes against proteolytic attack at the same time that it triggers their release under mild acidic conditions, usually present in many tumoral tissues. These enzyme nanocapsules have been attached on the surface of mesoporous silica nanoparticles, as nanocarrier model, showing a significatively higher penetration of the nanoparticles within 3D collagen matrices which housed human osteosarcoma cells (HOS). This strategy can improve the therapeutic efficacy of the current nanomedicines, allowing a more homogeneous and deeper distribution of the therapeutic nanosystems in cancerous tissues. © 2015 American Chemical Society.


Pueyo E.,University of Oxford | Pueyo E.,University of Zaragoza | Pueyo E.,Research Center Biomedica En Red Of Bioingenieria | Husti Z.,University of Szeged | And 8 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2010

Protracted QT interval (QTI) adaptation to abrupt heart rate (HR) changes has been identified as a clinical arrhythmic risk marker. This study investigates the ionic mechanisms of QTI rate adaptation and its relationship to arrhythmic risk. Computer simulations and experimental recordings in human and canine ventricular tissue were used to investigate the ionic basis of QTI and action potential duration (APD) to abrupt changes in HR with a protocol commonly used in clinical studies. The time for 90% QTI adaptation is 3.5 min in simulations, in agreement with experimental and clinical data in humans. APD adaptation follows similar dynamics, being faster in midmyocardial cells (2.5 min) than in endocardial and epicardial cells (3.5 min). Both QTI and APD adapt in two phases following an abrupt HR change: a fast initial phase with time constant < 30 s, mainly related to L-type calcium and slow-delayed rectifier potassium current, and a second slow phase of >2 min driven by intracellular sodium concentration ([Na+]i) dynamics. Alterations in [Na +]i dynamics due to Na+/K+ pump current inhibition result in protracted rate adaptation and are associated with increased proarrhythmic risk, as indicated by action potential triangulation and faster L-type calcium current recovery from inactivation, leading to the formation of early afterdepolarizations. In conclusion, this study suggests that protracted QTI adaptation could be an indicator of altered [Na+]i dynamics following Na+/K+ pump inhibition as it occurs in patients with ischemia or heart failure. An increased risk of cardiac arrhythmias in patients with protracted rate adaptation may be due to an increased risk of early afterdepolarization formation. Copyright © 2010 the American Physiological Society.


Alcaine A.,Aragon Institute of Engineering Research | Alcaine A.,Research Center Biomedica En Red Of Bioingenieria | Soto-Iglesias D.,University Pompeu Fabra | Calvo M.,University of Barcelona | And 9 more authors.
IEEE Transactions on Biomedical Engineering | Year: 2014

Electroanatomical mapping (EAM) systems are commonly used in clinical practice for guiding catheter ablation treatments of common arrhythmias. In focal tachycardias, the ablation target is defined by locating the earliest activation area determined by the joint analysis of electrogram (EGM) signals at different sites. However, this is currently a manual time-consuming and experience-dependent task performed during the intervention and thus prone to stress-related errors. In this paper, we present an automatic delineation strategy that combines electrocardiogram (ECG) information with the wavelet decomposition of the EGM signal envelope to identify the onset of each EGM signal for activation mapping. Fourteen electroanatomical maps corresponding to ten patients suffering from non-tolerated premature ventricular contraction (PVC) beats and admitted for ablation procedure were used for evaluation. We compared the results obtained automatically with two types of manual annotations: one during the intervention by an expert technician (on-procedure) and other after the intervention (off-procedure), free from time and procedural constraints, by two other technicians. The automatic annotations show a significant correlation (0.95, p < 0.01) with the evaluation reference (off-procedure annotation sets combination) and has an error of 2.1 ± 10.9 ms, around the order of magnitude of the on-procedure annotations error (- 2.6 ± 6.8 ms). The results suggest that the proposed methodology could be incorporated into EAM systems to considerably reduce processing time during ablation interventions. © 2014 IEEE.


Rigat-Brugarolas L.G.,Institute for Bioengineering of Catalonia IBEC | Rigat-Brugarolas L.G.,Research Center Biomedica En Red Of Bioingenieria | Homs-Corbera A.,Institute for Bioengineering of Catalonia IBEC | Homs-Corbera A.,Research Center Biomedica En Red Of Bioingenieria | And 3 more authors.
RSC Advances | Year: 2015

We present a novel methodology to create in a simple, fast and cheap way an interpenetrating polymer network biomaterial, mixing 2-hydroxyethil methacrylate and poly(dimethylsiloxane), for long-lasting highly hydrophilic microfluidic device prototyping. The presented polymer could be potentially useful to develop point-of-care microfluidic diagnostic devices allowing blood displacement without exertion in microchannels while proving to have low biological analytes adhesion. © 2015 The Royal Society of Chemistry.


Rodriguez-Hernandez C.J.,Barcelona Institute for Research in Biomedicine | Rodriguez-Hernandez C.J.,Hospital Sant Joan Of Deu | Llorens-Agost M.,Institute Biologia Molecular Y Celular Of Plantas Upv Csic | Llorens-Agost M.,National University of Ireland | And 6 more authors.
FEBS Letters | Year: 2013

Both radiotherapy and most effective chemotherapeutic agents induce different types of DNA damage. Here we show that tungstate modulates cell response to DNA damaging agents. Cells treated with tungstate were more sensitive to etoposide, phleomycin and ionizing radiation (IR), all of which induce DNA double-strand breaks (DSBs). Tungstate also modulated the activation of the central DSB signalling kinase, ATM, in response to these agents. These effects required the functionality of the Mre11-Nbs1-Rad50 (MRN) complex and were mimicked by the inhibition of PP2A phosphatase. Therefore, tungstate may have adjuvant activity when combined with DNA-damaging agents in the treatment of several malignancies. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Baeza A.,Research Center Biomedica En Red Of Bioingenieria | Guisasola E.,Research Center Biomedica En Red Of Bioingenieria | Torres-Pardo A.,Complutense University of Madrid | Gonzalez-Calbet J.M.,Complutense University of Madrid | And 3 more authors.
Advanced Functional Materials | Year: 2014

A novel nanocarrier based on functionalized mesoporous silica nanoparticles able to transport a non-toxic pro-drug and the enzyme responsible for its activation is presented. This nanodevice is able to generate in situ cytotoxic species once accumulated in the tumoral cell. Enzymes are sensitive macromolecules which can suffer denaturalization in biological media due to the presence of proteases or other aggressive agents. Moreover, the direct attachment of enzymes to the silica surface can reduce their activity by conformational changes or active site blockage. For these reasons, in order to create a robust system able to work in living organisms, the enzymes are previously coated with a protective polymeric shell which allows the attachment on the silica surface preserving their activity. The efficacy of this hybrid nanodevice for antitumoral purposes is tested against several human tumoral cells as neuroblastoma and leukemia showing significant efficacy. It converts this device in a promising candidate for further in vivo studies for oncology therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Llamedo M.,University of Buenos Aires | Llamedo M.,Aragon Institute of Engineering Research | Llamedo M.,Research Center Biomedica En Red Of Bioingenieria | Khawaja A.,Biosigna GmbH | And 2 more authors.
IEEE Transactions on Information Technology in Biomedicine | Year: 2012

In this paper, we studied the improvement in heartbeat classification achieved by including information from multilead ECG recordings in a previously developed and validated classification model. This model includes features from the RR interval series and morphology descriptors for each lead calculated from the wavelet transform. The experiments were carried out in the INCART database, available in Physionet, and the generalization was corroborated in private and public databases. In all databases, the AAMI recommendations for class labeling and results presentation were followed. Different strategies to integrate the additional information available in the 12-leads were studied. The best performing strategy consisted in performing principal component analysis to the wavelet transform of the available ECG leads. The performance indices obtained for normal beats were sensitivity ( S) 98%, positive predictive value ( P +) 93%; for supraventricular beats, ( S) 86%, (P + ) 91%; and for ventricular beats (S) 90%, (P +) 90%. The generalization capability of the chosen strategy was confirmed by applying the classifier to other databases with different number of leads with comparable results. In conclusion, the performance of the reference two-lead classifier was improved by taking into account additional information from the 12-leads. © 1997-2012 IEEE.

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