Millora de la resposta elèctrica de films de polímers conductors mitjançant tècniques d'augment de la superfície específica

La finalitat d’aquest projecte és l’anàlisi i comparació de la resposta elèctrica de films de dos polímers conductors diferents, el PEDOT (poli-(3,4-etilendioxitiofé)) i el PNMPy (poli(N-metilpirrol)). Aquests polímers son generats per mitjà de l’electrodeposició per cronoamperometria (CA) de films de polímer i combinats amb una dispersió interna de microcristalls de sals solubles en aigua, formant tricapes de polímer – sal – polímer. La dissolució d’aquestes sals ens permetrà disposar d’una dispersió de nanobuits que augmentarien la superfície específica del film de polímer. La resposta elèctrica dels films de polímer s’analitza mitjançant tècniques electroquímiques com la cronopotenciometria (CP) i la ciclovoltamperometria (CV). Seguidament es realitza una caracterització morfològica del PNMPy i del PEDOT per mitjà de tècniques de microscòpia, tals com microscòpia electrònica de rastreig (SEM) i microscòpia per forces atòmiques (AFM). Finalment es realitza un estudi de l’efecte de l’aigua en els polímers. Per tant l’objectiu d’aquest projecte és determinar quina és la millor configuració de tricapa polímer – sal – polímer en base a l’anàlisi dels resultats obtinguts de les diferents proves realitzades

Endogenous brain pericytes are widely activated and contribute to mouse glioma microvasculature.

Glioblastoma multiforme (GBM) is the most common brain tumor in adults. It presents an extremely challenging clinical problem, and treatment very frequently fails due to the infiltrative growth, facilitated by extensive angiogenesis and neovascularization. Pericytes constitute an important part of the GBM microvasculature. The contribution of endogenous brain pericytes to the tumor vasculature in GBM is, however, unclear. In this study, we determine the site of activation and the extent of contribution of endogenous brain pericytes to the GBM vasculature. GL261 mouse glioma was orthotopically implanted in mice expressing green fluorescent protein (GFP) under the pericyte marker regulator of G protein signaling 5 (RGS5). Host pericytes were not only activated within the glioma, but also in cortical areas overlying the tumor, the ipsilateral subventricular zone and within the hemisphere contralateral to the tumor. The host-derived activated pericytes that infiltrated the glioma were mainly localized to the tumor vessel wall. Infiltrating GFP positive pericytes co-expressed the pericyte markers platelet-derived growth factor receptor-β (PDGFR-β) and neuron-glial antigen 2. Interestingly, more than half of all PDGFR-β positive pericytes within the tumor were contributed by the host brain. We did not find any evidence that RGS5 positive pericytes adopt another phenotype within glioma in this paradigm. We conclude that endogenous pericytes become activated in widespread areas of the brain in response to an orthotopic mouse glioma. Host pericytes are recruited into the tumor and constitute a major part of the tumor pericyte population

Peptide gel in a scaffold as a composite matrix for endothelial cells

[EN] The performance of a composite environment with human umbilical vein endothelial cells (HUVECs) has been studied to provide an in vitro proof of concept of their potential of being easily vascularized. These cells were seeded in 1 mm thick scaffolds whose pores had been filled with a self-assembling peptide gel, seeking to improve cell adhesion, and viability of these very sensitive cells. The combination of the synthetic elastomer poly(ethyl acrylate), PEA, scaffold and the RAD16-I peptide gel provides cells with a friendly ECM-like environment inside a mechanically resistant structure. Immunocytochemistry, flow cytometry and scanning electron microscopy were used to evaluate the cell cultures. The presence of the self-assembling peptide filling the pores of the scaffolds resulted in a truly 3D nanoscale context mimicking the extracellular matrix environment, and led to increased cells survival, proliferation as well as developed cell-cell contacts. The combined system consisting of PEA scaffolds and RAD16-I, is a very interesting approach as seems to enhance endothelization, which is the first milestone to achieve vascularized constructs. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3293-3302, 2015.Contract grant sponsor: European Commission FP7 project RECATABI; contract grant number: NMP3-SL-2009-229239 Contract grant sponsor: Spanish Ministerio de Ciencia e Innovacion; contract grant numbers: MAT2011-28791-C03-02 and -03 Contract grant sponsor: Spanish Ministry of Education through M. Arnal-Pastor; contract grant number: FPU 2009-1870Martínez Ramos, C.; Arnal Pastor, MP.; Vallés Lluch, A.; Monleón Pradas, M. (2015). Peptide gel in a scaffold as a composite matrix for endothelial cells. Journal of Biomedical Materials Research Part A. 103(10):3293-3302. https://doi.org/10.1002/jbm.a.35462S329333021031

Discovery of microvascular miRNAs using public gene expression data: miR-145 is expressed in pericytes and is a regulator of Fli1

International audienceBACKGROUND: A function for the microRNA (miRNA) pathway in vascular development and angiogenesis has been firmly established. miRNAs with selective expression in the vasculature are attractive as possible targets in miRNA-based therapies. However, little is known about the expression of miRNAs in microvessels in vivo. Here, we identified candidate microvascular-selective miRNAs by screening public miRNA expression datasets. METHODS: Bioinformatics predictions of microvascular-selective expression were validated with real-time quantitative reverse transcription PCR on purified microvascular fragments from mouse. Pericyte expression was shown with in situ hybridization on tissue sections. Target sites were identified with 3' UTR luciferase assays, and migration was tested in a microfluid chemotaxis chamber. RESULTS: miR-145, miR-126, miR-24, and miR-23a were selectively expressed in microvascular fragments isolated from a range of tissues. In situ hybridization and analysis of Pdgfb retention motif mutant mice demonstrated predominant expression of miR-145 in pericytes. We identified the Ets transcription factor Friend leukemia virus integration 1 (Fli1) as a miR-145 target, and showed that elevated levels of miR-145 reduced migration of microvascular cells in response to growth factor gradients in vitro. CONCLUSIONS: miR-126, miR-24 and miR-23a are selectively expressed in microvascular endothelial cells in vivo, whereas miR-145 is expressed in pericytes. miR-145 targets the hematopoietic transcription factor Fli1 and blocks migration in response to growth factor gradients. Our findings have implications for vascular disease and provide necessary information for future drug design against miRNAs with selective expression in the microvasculature

Injectable Peptide Decorated Functional Nanofibrous Hollow Microspheres to Direct Stem Cell Differentiation and Tissue Regeneration

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110559/1/adfm201402618-sup-0001-S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110559/2/adfm201402618.pd

The mechanical stimulation of cells in 3D culture within a self-assembling peptide hydrogel

The aim of this present study was to provide a scaffold as a tool for the investigation of the effect of mechanical stimulation on three-dimensionally cultured cells. For this purpose, we developed an artificial self-assembling peptide (SPG-178) hydrogel scaffold. The structural properties of the SPG-178 peptide were confirmed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and transmission electron microscopy (TEM). The mechanical properties of the SPG-178 hydrogel were studied using rheology measurements. The SPG-178 peptide was able to form a stable, transparent hydrogel in a neutral pH environment In the SPG-178 hydrogel, mouse skeletal muscle cells proliferated successfully (increased by 12.4 +/- 1.5 times during 8 days of incubation; mean +/- SEM). When the scaffold was statically stretched, a rapid phosphorylation of ERK was observed (increased by 2.8 +/- 0.2 times; mean +/- SEM). These results demonstrated that the developed self-assembling peptide gel is non-cytotoxic and is a suitable tool for the investigation of the effect of mechanical stimulation on three-dimensional cell culture

In vitro development of bioimplants made up of elastomeric scaffolds with peptide gel filling seeded with human subcutaneous adipose tissue-derived progenitor cells

[EN] Myocardial tissue lacks the ability to regenerate itself significantly following a myocardial infarction. Thus, new strategies that could compensate this lack are of high interest. Cardiac tissue engineering (CTE) strategies are a relatively new approach that aims to compensate the tissue loss using combination of biomaterials, cells and bioactive molecules. The goal of the present study was to evaluate cell survival and growth, seeding capacity and cellular phenotype maintenance of subcutaneous adipose tissue-derived progenitor cells in a new synthetic biomaterial scaffold platform. Specifically, here we tested the effect of the RAD16-I peptide gel in microporous poly(ethyl acrylate) polymers using two-dimensional PEA films as controls. Results showed optimal cell adhesion efficiency and growth in the polymers coated with the self-assembling peptide RAD16-I. Importantly, subATDPCs seeded into microporous PEA scaffolds coated with RAD16-I maintained its phenotype and were able to migrate outwards the bioactive patch, hopefully toward the infarcted area once implanted. These data suggest that this bioimplant (scaffold/RAD16-I/cells) can be suitable for further in vivo implantation with the aim to improve the function of affected tissue after myocardial infarction. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3419-3430, 2015.Contract grant sponsor: European Union Seventh Framework Programme; contract grant number: 229239Castells-Sala, C.; Martínez Ramos, C.; Vallés Lluch, A.; Monleón Pradas, M.; Semino, C. (2015). In vitro development of bioimplants made up of elastomeric scaffolds with peptide gel filling seeded with human subcutaneous adipose tissue-derived progenitor cells. Journal of Biomedical Materials Research Part A. 103(11):3419-3430. https://doi.org/10.1002/jbm.a.35482S3419343010311Persidis, A. (1999). 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Combining self-assembling peptide gels with three-dimensional elastomer scaffolds

[EN] Some of the problems raised by the combination of porous scaffolds and self-assembling peptide (SAP) gels as constructs for tissue engineering applications are addressed for the first time. Scaffolds of poly(- ethyl acrylate) and the SAP gel RAD16-I were employed. The in situ gelation of the SAP gel inside the pores of the scaffolds was studied. The scaffold-cum-gel constructs were characterized morphologically, physicochemically and mechanically. The possibility of incorporating an active molecule (bovine serum albumin, taken here as a model molecule for others) in the gel within the scaffold’s pores was assessed, and the kinetics of its release in phosphate-buffered saline was followed. Cell seeding and colonization of these constructs were preliminarily studied with L929 fibroblasts and subsequently checked with sheep adipose-tissue-derived stem cells intended for further preclinical studies. Static (conventional) and dynamically assisted seedings were compared for bare scaffolds and the scaffold-cum-gel constructs. The SAP gel inside the pores of the scaffold significantly improved the uniformity and density of cell colonization of the three-dimensional (3-D) structure. These constructs could be of use in different advanced tissue engineering applications, where, apart from a cell-friendly extracellular matrix -like aqueous environment, a larger-scale 3-D structure able to keep the cells in a specific place, give mechanical support and/or conduct spatially the tissue growth could be required.The authors acknowledge funding through the European Commission FP7 project RECATABI (NMP3-SL-2009-229239), and from the Spanish Ministerio de Ciencia e Innovacion through projects MAT2011-28791-C03-02 and -03. Dr. J.C. Chachques (Hopital Europeen Georges Pompidou, Paris) is thanked for providing the ASCs employed in this study. MMP acknowledges support of CIBER-BBN initiative, financed by Institut de Salud Carlos III (Spain) with the assistance of the European Regional Development Fund.Vallés Lluch, A.; Arnal Pastor, MP.; Martínez Ramos, C.; Vilariño Feltrer, G.; Vikingsson, L.; Castells Sala, C.; Semino, CE.... (2013). Combining self-assembling peptide gels with three-dimensional elastomer scaffolds. Acta Biomaterialia. 9(12):9451-9460. https://doi.org/10.1016/j.actbio.2013.07.038S9451946091

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe