A human plasma derived supplement preserves function of human vascular cells in absence of fetal bovine serum

Current techniques for cell culture routinely use animal-derived components. Fetal bovine serum (FBS) is the most widely applied supplement, but it often displays significant batch-to-batch variations and is generally not suitable for clinical applications in humans. A robust and xeno-free alternative to FBS is of high interest for cellular therapies, from early in vitro testing to clinical trials in human subjects. In the current work, a highly consistent human plasma derived supplement (SCC) has been tested, as a potential substitute of FBS in primary human vascular cells culture. Our results show that SCC is able to support proliferation, preserve cellular morphology and potentiate functionality analogously to FBS. We conclude that SCC is a viable substitute of FBS for culture and expansion of cells in advanced therapies using human vascular cells and fibroblasts

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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Development of Bioactive Patch for Maintenance of Implanted Cells at the Myocardial Infarcted Site

[EN] Ischemia produced as a result of myocardial infarction might cause moderate or severe tissue death. Studies under development propose grafting stem cells into the affected area and we hypothesize that this mechanism could be enhanced by the application of a "bioactive implant." The implant herein proposed consists of a thin porous elastomeric membrane, filled with self-assembling nanofibers and human subcutaneous adipose tissue derived progenitor cells. We describe the development and characterization of two elastomeric membranes: poly(ethyl acrylate) (PEA) and poly(caprolactone 2-(methacryloyloxy) ethyl ester) (PCLMA). Both are a good material support to deliver cells within a soft self-assembling peptide and are elastic enough to withstand the stresses arising from the heartbeat. Both developed composites (PEA and PCLMA, combined with self-assembling peptide) equally facilitate the propagation of electrical pulses and maintain their genetic profile of the seeded cells. Preliminary studies with small animal models suggest that, at short times, the bioimplant shows good adhesion with the myocardium. After three days cells loaded in the patch remain alive at the implanted site. We propose that the bioactive patch (elastomeric membranes with self-assembling peptide and cells) could increase the efficacy of future cardiac cell therapy by improving cell immobilization and survival at the affected site.The authors wish to thank the Department of Cardiac Surgery (Hospital Germans Trias i Pujol, Badalona) for their collaboration in obtaining human samples, Dr. Bago for his kind contribution in the cell transduction process and BLI analysis, and Joan Gilabert from Biomaterials Laboratory (GEMAT, IQS-School of Engineering) who kindly helped them with wettability measurements. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant agreement no. 229239. This work was also supported by Grants from Ministerio de Educacion y Ciencia (SAF2011-30067-C02-01 and M. Arnal-Pastor FPU 2009-1870 grant), Red de Terapia Celular-TerCel (RD12/0019/0029), Red Cardio-vascular (RD12/0042/0047), and Fundacio La Marato de TV3 (122232).Castells-Sala, C.; Vallés Lluch, A.; Soler-Botija, C.; Arnal Pastor, MP.; Martínez Ramos, C.; Fernandez-Muinos, T.; Mari-Buye, N.... (2015). Development of Bioactive Patch for Maintenance of Implanted Cells at the Myocardial Infarcted Site. Journal of Nanomaterials. (804017). https://doi.org/10.1155/2015/804017S80401

Descriptive analysis of childbirth healthcare costs in an area with high levels of immigration in Spain

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to estimate the cost of childbirth in a teaching hospital in Barcelona, Spain, including the costs of prenatal care, delivery and postnatal care (3 months). Costs were assessed by taking into account maternal origin and delivery type.</p> <p>Methods</p> <p>We performed a cross-sectional study of all deliveries in a teaching hospital to mothers living in its catchment area between October 2006 and September 2007. A process cost analysis based on a full cost accounting system was performed. The main information sources were the primary care program for sexual and reproductive health, and hospital care and costs records. Partial and total costs were compared according to maternal origin and delivery type. A regression model was fit to explain the total cost of the childbirth process as a function of maternal age and origin, prenatal care, delivery type, maternal and neonatal severity, and multiple delivery.</p> <p>Results</p> <p>The average cost of childbirth was 4,328€, with an average of 18.28 contacts between the mother or the newborn and the healthcare facilities. The delivery itself accounted for more than 75% of the overall cost: maternal admission accounted for 57% and neonatal admission for 20%. Prenatal care represented 18% of the overall cost and 75% of overall acts. The average overall cost was 5,815€ for cesarean sections, 4,064€ for vaginal instrumented deliveries and 3,682€ for vaginal non-instrumented deliveries (p < 0.001). The regression model explained 45.5% of the cost variability. The incremental cost of a delivery through cesarean section was 955€ (an increase of 31.9%) compared with an increase of 193€ (6.4%) for an instrumented vaginal delivery. The incremental cost of admitting the newborn to hospital ranged from 420€ (14.0%) to 1,951€ (65.2%) depending on the newborn's severity. Age, origin and prenatal care were not statistically significant or economically relevant.</p> <p>Conclusions</p> <p>Neither immigration nor prenatal care were associated with a substantial difference in costs. The most important predictors of cost were delivery type and neonatal severity. Given the impact of cesarean sections on the overall cost of childbirth, attempts should be made to take into account its higher cost in the decision of performing a cesarean section.</p

Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

The potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial. Viremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridial es. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size. The present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption. The online version contains supplementary material available at 10.1186/s40168-022-01247-6

Channeled polymeric scaffolds with polypeptide gel filling for lengthwise guidance of neural cells

CNS damages are often irreversible since neurons of the central nervous system are unable to regenerate after an injury. As a new strategy within the nervous system tissue engineering, multifunctional systems based on two different biomaterials to support axonal guidance in damaged connective tracts have been developed herein. These systems are composed of a channeled scaffold made of ethyl acrylate and hydroxyethyl acrylate copolymer, P(EA-co-HEA), with parallel tubular micropores, combined with an injectable and in situ gelable self-assembling polypeptide (RAD16-I) as pores filler. The polymer scaffold is intended to provide a three-dimensional context for axon growth; subsequently, its morphology and physicochemical parameters have been determined by scanning electron microscopy, density measurements and compression tests. Besides, the hydrogel acts as a cell-friendly nanoenvironment while it creates a gradient of bioactive molecules (nerve growth factor, NGF) along the scaffolds channels; the chemotactic effect of NGF has been evaluated by a quantitative ELISA assay. These multifunctional systems have shown ability to keep circulating NGF, as well as proper short-term in vitro biological response with glial cells and neural progenitors.The authors acknowledge funding through the Spanish Ministerio de Ciencia e Innovacion (MAT2011-28791-C03-02 and -03). Dr. J.M. Garcia Verdugo (Department of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutive Biology, Universitat de Valencia) is thanked for kindly providing the cells employed in this work.Conejero García, Á.; Vilarino-Feltrer, G.; Martínez Ramos, C.; Monleón Pradas, M.; Vallés Lluch, A. (2015). Channeled polymeric scaffolds with polypeptide gel filling for lengthwise guidance of neural cells. European Polymer Journal. 70:331-341. doi:10.1016/j.eurpolymj.2015.07.033S3313417

Tracking positive and negative effects of inequality on long-run growth

Despite extensive research controversy remains on the effects of income inequality on economic growth. The literature proposes several transmission channels through which these effects may occur and even the existence of two different forms of inequality. However, empirical studies have not generally distinguished between these channels, nor have they considered the two forms of inequality and their separate effects on growth. In this paper we review the theory and the evidence of the transmission channels through which inequality influences growth. We contribute to the literature by using a system of recursive equations, following a control function approach, to empirically assess the relevance of these channels and to differentiate between two forms of inequality. In a single model, we capture both a negative and a positive effect of inequality on long-run economic growt

Agglomeration, Inequality and Economic Growth (WP)

The impact of income inequality on economic growth is dependent on several factors, including the time horizon considered, the initial level of income and its initial distribution. Yet, as growth and inequality are also uneven across space, it is also pertinent to consider the effects of the geographical agglomeration of economic activity. Moreover, it would also seem pertinent to consider not just the levels of inequality and agglomeration, but also the changes they undergo -i.e., their within-country evolution- and how these two processes interact with each other. By applying different econometric specifications and by introducing different measures of agglomeration at country level -specifically, urbanization and urban concentration rates-, this study analyzes how inequality and agglomeration -both their levels and their evolution- influence economic growth in function of the country’s level of development and its initial income distribution. Our results suggest, in line with previous studies, that while high inequality levels are a limiting factor for long-run growth, increasing inequality and increasing agglomeration have the potential to enhance growth in low-income countries where income distribution remains relatively equal, but can result in congestion diseconomies in high-income countries, especially if income distribution becomes particularly unequal

Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival.</p> <p>Methods</p> <p>A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers.</p> <p>Results</p> <p>A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively) or with other cancers (10, 19, and 15 genes, respectively) and the rest (16, 4, and 10 genes, respectively) are novel associations. <it>Pik3r1</it>, <it>E2f3, Akr1c3</it>, <it>Csf1</it>, <it>Jag2</it>, <it>Plcg1</it>, <it>Rpl37a</it>, <it>Sod2</it>, <it>Topors</it>, <it>Hras</it>, <it>Mdm2, Camk2g</it>, <it>Fstl1</it>, <it>Il13ra1</it>, <it>Mtap </it>and <it>Tp53 </it>were associated with multiple survival events.</p> <p>Most genes (from 90 to 96%) were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for <it>Syne1</it>, <it>Pdcd4</it>, <it>Ighg1</it>, <it>Tgfa</it>, <it>Pla2g7</it>, and <it>Paics</it>. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. <it>C2</it>, <it>Egfr</it>, <it>Prkcb</it>, <it>Igf2bp3</it>, and <it>Gdf10 </it>had gender-dependent associations; <it>Sox10</it>, <it>Rps20</it>, <it>Rab31</it>, and <it>Vav3 </it>had race-dependent associations; <it>Chi3l1</it>, <it>Prkcb</it>, <it>Polr2d</it>, and <it>Apool </it>had therapy-dependent associations. Biological processes associated glioblastoma survival included morphogenesis, cell cycle, aging, response to stimuli, and programmed cell death.</p> <p>Conclusions</p> <p>Known biomarkers of glioblastoma survival were confirmed, and new general and clinical-dependent gene profiles were uncovered. The comparison of biomarkers across glioblastoma phases and functional analyses offered insights into the role of genes. These findings support the development of more accurate and personalized prognostic tools and gene-based therapies that improve the survival and quality of life of individuals afflicted by glioblastoma multiforme.</p

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