Francois Rossi | European Commission Joint Research Centre (original) (raw)
Papers by Francois Rossi
Surface and Coatings Technology, 2011
In this work, we investigate the surface reactivity of substrates coated with thin layers (estima... more In this work, we investigate the surface reactivity of substrates coated with thin layers (estimated thickness ≤ 30 nm) of plasma polymerized allylamine films (PPAA), an amine-functionalized polymer deposited by plasma-enhanced chemical vapor deposition (PECVD) with radiofrequency (RF) discharges. Our results show that very thin layers, or islands, can retain on their surface molecules that are able to react through their NH 2 functions. We have tested and assessed by X-Ray Electron Spectroscopy (XPS) and Quartz Crystal Microbalance (QCM) the surface density of chemical functions vs. layer thicknesses by using chemical derivatization with two types of agents: imine formation by a reaction of primary amine from the coating with aldehyde (Pentafluorobenzaldehyde, PFBA) and amide-bond formation by reaction with an activated carboxylic group (Succinimidyl Succinate Terminated Polyethylene glycol, EGSS). Results show that the PPAA coatings-even for very thin layers of a few nanometers-promote the chemisorption of the tagging molecules. The aging under air and evolution of reactive amine surface concentration with time under air are also presented.
Toxicology in Vitro, 2016
Link to publication on Research at Birmingham portal General rights Unless a licence is specified... more Link to publication on Research at Birmingham portal General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. • Users may freely distribute the URL that is used to identify this publication. • Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. • User may use extracts from the document in line with the concept of 'fair dealing' under the Copyright, Designs and Patents Act 1988 (?) • Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.
PLOS ONE, 2015
Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable... more Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO 2 NMs with different surface chemistryhydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnOuncoated (NM-110) and coated with triethoxycapryl silane (NM-111) and two SiO 2 NMs produced by two different manufacturing techniquesprecipitated (NM-200) and pyrogenic (NM-203). Cell
Micro and Nanosystemse, 2009
Arrays of human umbilical cord blood-neural stem cells have been patterned in high density at sin... more Arrays of human umbilical cord blood-neural stem cells have been patterned in high density at single cell resolution. Pre-patterns of adhesive molecules, i.e. fibronectin and poly-L-lysine, have been produced on anti-adhesive poly (ethylene) oxide films deposited by plasma-enhanced chemical vapour deposition, which prevents cell adsorption. The structures consisted of adhesive squares and lines with 10 m lateral dimensions, which correspond approximately to the size of one cell nucleus, separated by 10 m anti-adhesive gap. The stem cells cultured on these platforms redistribute their cytoplasm on the permitted areas. Spherical cells were deposited on the square patterns in a single cell mode, while on the lines they spread longitudinally; the extent of elongation being dependent on the specific (fibronectin) or non-specific (poly-L-lysine) attachment biomolecule. The cell patterns were retained up to 12 days, which will be useful for recording statistical data of individual chronic responses to chemical, physical or physiologically relevant stimuli.
Page 1. 183 7 Preventing Biofilm Formation on Biomedical Surfaces Virendra Kumar, Hubert Rauscher... more Page 1. 183 7 Preventing Biofilm Formation on Biomedical Surfaces Virendra Kumar, Hubert Rauscher, Frédéric Brétagnol, Farzaneh Arefi-Khonsari, Jerome Pulpytel, Pascal Colpo, and Franc¸ ois Rossi 7.1 Bacterial Adhesion to Biomaterials: Biofilm Formation ...
Toxicology Letters, 2015
Biological effects (toxicity, uptake and changes in gene expression patterns) on Caco-2 cells of ... more Biological effects (toxicity, uptake and changes in gene expression patterns) on Caco-2 cells of citrate-stabilized 5 nm and 30 nm AuNPs were compared. Exposure to 5 nm AuNPs had much stronger effect on gene expression as compared to treatment with 30 nm AuNPs. Nrf2 signaling stress response was among the highly activated pathways.
Particle and Fibre Toxicology, 2013
Background Cobalt-ferrite nanoparticles (Co-Fe NPs) are attractive for nanotechnology-based thera... more Background Cobalt-ferrite nanoparticles (Co-Fe NPs) are attractive for nanotechnology-based therapies. Thus, exploring their effect on viability of seven different cell lines representing different organs of the human body is highly important. Methods The toxicological effects of Co-Fe NPs were studied by in-vitro exposure of A549 and NCIH441 cell-lines (lung), precision-cut lung slices from rat, HepG2 cell-line (liver), MDCK cell-line (kidney), Caco-2 TC7 cell-line (intestine), TK6 (lymphoblasts) and primary mouse dendritic-cells. Toxicity was examined following exposure to Co-Fe NPs in the concentration range of 0.05 -1.2 mM for 24 and 72 h, using Alamar blue, MTT and neutral red assays. Changes in oxidative stress were determined by a dichlorodihydrofluorescein diacetate based assay. Data analysis and predictive modeling of the obtained data sets were executed by employing methods of Knowledge Discovery from Data with emphasis on a decision tree model (J48). Results Different dos...
Toxicology Letters, 2014
We report here an in vitro evaluation of silica nanoparticle uptake by lung epithelial cells (A54... more We report here an in vitro evaluation of silica nanoparticle uptake by lung epithelial cells (A549), the cytotoxic effect of the particles and we propose autophagy as possible survival strategy. The effect of surface charge, serum proteins and the influence of inhibitors on the uptake of 20 nm monodispersed nanoparticles with various functional groups are discussed. Uptake rate of the particles with various functional groups is demonstrated to be similar in the presence of serum proteins, while the uptake rate ranking is COOH>NH2>OH under serum free conditions. Our results suggest an actin-dependent, macropinocytotic uptake process that was also confirmed by scanning and transmission electron microscopy. In spite of the intensive active uptake, significant cytotoxic effect is detected only at relatively high concentrations (above 250 μg/mL). Blebbing of the cell surface is observed already at 5h of exposure and is shown to be related to autophagy rather than apoptotic cell death. The A549 cells display elevated levels of autophagosomes, however they do not express typical apoptosis markers such as increased amount of active caspase-3 and release of mitochondrial cytochrome C. Based on these results, we propose here an autophagic activity and cross-talk between autophagic and apoptotic pathways as a mechanism allowing the survival of A549 cells under exposure to silica nanoparticles.
Toxicology Letters, 2010
In this work, we present a complete physicochemical characterization of multi-wall carbon nanotub... more In this work, we present a complete physicochemical characterization of multi-wall carbon nanotubes (mwCNTs) in order to assess their potential toxicological effects in in vitro cell models using Colony Forming Efficiency (CFE) assay. We verified that Dimethyl Sulfoxide (DMSO) was a more suitable solvent to disperse mwCNTs compared to culture medium guaranteeing reproducibility in the preparation of testing dilutions. The CFE assay was carried out on five mammalian cell lines representing the potentially exposed and/or target organs for nanomaterials (lung, liver, kidney, intestine, skin), as well as on mouse fibroblasts cell line, which usually is considered a sensitive model to verify in vitro cytotoxicity of test compounds. A statistically significant toxic effect was found only in human alveolar basal epithelial cells and immortalized mouse fibroblasts, for which the interaction between mwCNTs and cells was additionally studied by Atomic Force and Scanning Electron Microscopy. In this study, we considered and suggested the CFE assay as a promising test for screening studies of cytotoxicity. In addition, combining in vitro tests with physicochemical analysis, this work underlines basic points to be considered when research on nanomaterials has to be carried out, to set up, in our opinion, well-defined and suitable experimental planning and procedures.
Toxicology Letters, 2008
Recent advances in human stem cell biology provide a new opportunity for the development of hepat... more Recent advances in human stem cell biology provide a new opportunity for the development of hepatocyte-like cell lines suitable for use in in vitro toxicity assays. Human embryonic stem cells, by virtue of their combined potential for self-renewal and pluripotency, appear to be particularly useful for the generation of large numbers of cells of specific lineage. Required features of these cells include a fully differentiated phenotype capable of representing in situ hepatocyte functionality, particularly with respect to xenobiotic metabolism and transport. Progress to date demonstrates partial success, but further improvements are still required. Additional challenges include the development of methodologies to enable scaling up, selection and purification, together with extensive validation work to demonstrate the practical utility of the cells for toxicological applications. New areas of research such as direct somatic cell reprogramming have introduced further possibilities for the wider exploitation of stem cell biology in toxicology.
Toxicology, 2010
Stem cell technology combined with emerging surface nano/micro-technologies provides a new tool f... more Stem cell technology combined with emerging surface nano/micro-technologies provides a new tool for better understanding of the mechanisms involved in cell fate decisions and compound-induced adverse reactions. This article provides state-of-the-art on the development of modern multiparameter bio-tests based on interactions between neural stem cells derived from human cord blood and bioengineered surfaces. Cell growth platforms with controlled content, geometry and spatial distribution of bioactive and stem cell attractive areas were fabricated either by micro-contact printing or piezoelectric spotting of polycationic biomolecules or extracellular matrix proteins (ECM) on cell-repellent surfaces. HUCB-NSCs were shown to adhere, differentiate and respond to neurotoxic MeHgCl on functional domains in a manner dependent on protein type and concentration, cell density and serum conditions. While receptor-mediated interactions with ECM proteins under absence of serum promote neuronal differentiation, non-specific adhesion to polycationic molecules maintain cells attached to the surface in non-differentiated stage. Functional domains were further engineered to create "smart" microenvironment by immobilizing to the surface signaling molecules together with ECM proteins. Stimulation of selected intracellular pathways by molecules of Wnt, Shh, CNTF or Notch type resulted in differentiation of HUCB-NSC to either neuronal or astroglial lineage. Sensor techniques applied to HUCB-NSC included measurements of electrical activity using multielectrode array chips. Spontaneous electrical field potentials of HUCB-NSCs were dependent upon developmental stage of tested cells. Bioengineered surfaces, on protein microarrays and micro-electrode array chips provide a novel approach to the multiparameter bio-tests by adding an important information on the sensitivity of certain molecular pathways and functional cellular responses to selected neurotoxins.
Toxicological Sciences, 2011
The toxicological effects of cobalt nanoparticles (Co-NPs) aggregates were examined and compared ... more The toxicological effects of cobalt nanoparticles (Co-NPs) aggregates were examined and compared with those of cobalt ions (Co-ions) using six different cell lines representing lung, liver, kidney, intestine, and the immune system. Dose-response curves were studied in the concentration range of 0.05-1.0mM, employing 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide test, neutral red, and Alamar blue as end point assays following exposures for 48 and 72 h. Data analysis and predictive modeling of the obtained data sets were executed by employing a decision tree model (J48), where training and validation were carried out by an iterative process. It was established, as expected, that concentration is the highest rank parameter. This is because concentration parameter provides the highest information gain with respect to toxicity. The second-rank parameter emerged to be either the compound type (Co-ions or Co-NPs) or the cell model, depending on the concentration range. The third and the lowest rank in the model was exposure duration. The hierarchy of cell sensitivity toward cobalt ions was found to obey the following sequence of cell lines: A549 > MDCK > NCIH441 > Caco-2 > HepG2 > dendritic cells (DCs), with A549 being the most sensitive cell line and primary DCs were the least sensitive ones. However, a different hierarchy pattern emerged for Co-NPs: A549 5 MDCK 5 NCIH441 5 Caco-2 > DCs > HepG2. The overall findings are in line with the hypothesis that the toxic effects of aggregated cobalt NPs are mainly due to cobalt ion dissolution from the aggregated NPs.
Soft Matter, 2009
Microarrays of fibronectin and other extracellular matrix (ECM) proteins were fabricated on plasm... more Microarrays of fibronectin and other extracellular matrix (ECM) proteins were fabricated on plasma-deposited poly(ethyleneoxide) (PEO-like) film coated glass slides to study adhesion of stem cells. The arrays were generated by using a non-contact printing technology. The ...
Sensors and Actuators B: Chemical, 2007
... a Institute for Health and Consumer Protection (IHCP), Joint Research Centre, TP 203, I-21020... more ... a Institute for Health and Consumer Protection (IHCP), Joint Research Centre, TP 203, I-21020 ... acquisition time was kept below 10 min to avoid any possible X-ray induced damage ... For theseexperiments, the different coatings have been deposited on TCPS Petri dishes and a ...
Plasma Processes and Polymers, 2014
This study points out how the plasma modification of PCL porous scaffolds, produced by Solvent Ca... more This study points out how the plasma modification of PCL porous scaffolds, produced by Solvent Casting/Particulate Leaching, may enhance their biocompatibility. A C 2 H 4 /N 2 plasma deposition followed by a H 2 plasma treatment was used to increase the hydrophilicity of the whole scaffold to support osteoblast cell proliferation, both outside and inside the scaffold. A better cell growth was obtained on plasma modified scaffolds.
Plasma Processes and Polymers, 2006
Plasma Processes and Polymers, 2010
Nanotoxicology, 2012
In this work we investigated the toxicological effects of nude and chemically functionalised (-NH... more In this work we investigated the toxicological effects of nude and chemically functionalised (-NH(2), -OH and -COOH groups) multiwall carbon nanotubes (mwCNTs) using immortalised mouse fibroblasts cell line (Balb/3T3) as in vitro model, alternative to the use of animals, to assess basal cytotoxicity, carcinogenic potential, genotoxicity and cell interaction of nanomaterials (NM). Combining in vitro tests such as cell transformation assay and micronucleus with physicochemical and topological analysis, we obtained results showing no cytotoxicity and genotoxicity. Carcinogenic potential and mwCNTs interaction with cells were instead evident. We stressed the importance that different toxicological end points have to be considered when studying NM, therefore, assays able to detect long-term effects, such as carcinogenicity, must be taken into account together with a panel of tests able to detect more immediate effects like basal cytotoxicity or genotoxicity.
Surface and Coatings Technology, 2011
In this work, we investigate the surface reactivity of substrates coated with thin layers (estima... more In this work, we investigate the surface reactivity of substrates coated with thin layers (estimated thickness ≤ 30 nm) of plasma polymerized allylamine films (PPAA), an amine-functionalized polymer deposited by plasma-enhanced chemical vapor deposition (PECVD) with radiofrequency (RF) discharges. Our results show that very thin layers, or islands, can retain on their surface molecules that are able to react through their NH 2 functions. We have tested and assessed by X-Ray Electron Spectroscopy (XPS) and Quartz Crystal Microbalance (QCM) the surface density of chemical functions vs. layer thicknesses by using chemical derivatization with two types of agents: imine formation by a reaction of primary amine from the coating with aldehyde (Pentafluorobenzaldehyde, PFBA) and amide-bond formation by reaction with an activated carboxylic group (Succinimidyl Succinate Terminated Polyethylene glycol, EGSS). Results show that the PPAA coatings-even for very thin layers of a few nanometers-promote the chemisorption of the tagging molecules. The aging under air and evolution of reactive amine surface concentration with time under air are also presented.
Toxicology in Vitro, 2016
Link to publication on Research at Birmingham portal General rights Unless a licence is specified... more Link to publication on Research at Birmingham portal General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. • Users may freely distribute the URL that is used to identify this publication. • Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. • User may use extracts from the document in line with the concept of 'fair dealing' under the Copyright, Designs and Patents Act 1988 (?) • Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.
PLOS ONE, 2015
Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable... more Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO 2 NMs with different surface chemistryhydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnOuncoated (NM-110) and coated with triethoxycapryl silane (NM-111) and two SiO 2 NMs produced by two different manufacturing techniquesprecipitated (NM-200) and pyrogenic (NM-203). Cell
Micro and Nanosystemse, 2009
Arrays of human umbilical cord blood-neural stem cells have been patterned in high density at sin... more Arrays of human umbilical cord blood-neural stem cells have been patterned in high density at single cell resolution. Pre-patterns of adhesive molecules, i.e. fibronectin and poly-L-lysine, have been produced on anti-adhesive poly (ethylene) oxide films deposited by plasma-enhanced chemical vapour deposition, which prevents cell adsorption. The structures consisted of adhesive squares and lines with 10 m lateral dimensions, which correspond approximately to the size of one cell nucleus, separated by 10 m anti-adhesive gap. The stem cells cultured on these platforms redistribute their cytoplasm on the permitted areas. Spherical cells were deposited on the square patterns in a single cell mode, while on the lines they spread longitudinally; the extent of elongation being dependent on the specific (fibronectin) or non-specific (poly-L-lysine) attachment biomolecule. The cell patterns were retained up to 12 days, which will be useful for recording statistical data of individual chronic responses to chemical, physical or physiologically relevant stimuli.
Page 1. 183 7 Preventing Biofilm Formation on Biomedical Surfaces Virendra Kumar, Hubert Rauscher... more Page 1. 183 7 Preventing Biofilm Formation on Biomedical Surfaces Virendra Kumar, Hubert Rauscher, Frédéric Brétagnol, Farzaneh Arefi-Khonsari, Jerome Pulpytel, Pascal Colpo, and Franc¸ ois Rossi 7.1 Bacterial Adhesion to Biomaterials: Biofilm Formation ...
Toxicology Letters, 2015
Biological effects (toxicity, uptake and changes in gene expression patterns) on Caco-2 cells of ... more Biological effects (toxicity, uptake and changes in gene expression patterns) on Caco-2 cells of citrate-stabilized 5 nm and 30 nm AuNPs were compared. Exposure to 5 nm AuNPs had much stronger effect on gene expression as compared to treatment with 30 nm AuNPs. Nrf2 signaling stress response was among the highly activated pathways.
Particle and Fibre Toxicology, 2013
Background Cobalt-ferrite nanoparticles (Co-Fe NPs) are attractive for nanotechnology-based thera... more Background Cobalt-ferrite nanoparticles (Co-Fe NPs) are attractive for nanotechnology-based therapies. Thus, exploring their effect on viability of seven different cell lines representing different organs of the human body is highly important. Methods The toxicological effects of Co-Fe NPs were studied by in-vitro exposure of A549 and NCIH441 cell-lines (lung), precision-cut lung slices from rat, HepG2 cell-line (liver), MDCK cell-line (kidney), Caco-2 TC7 cell-line (intestine), TK6 (lymphoblasts) and primary mouse dendritic-cells. Toxicity was examined following exposure to Co-Fe NPs in the concentration range of 0.05 -1.2 mM for 24 and 72 h, using Alamar blue, MTT and neutral red assays. Changes in oxidative stress were determined by a dichlorodihydrofluorescein diacetate based assay. Data analysis and predictive modeling of the obtained data sets were executed by employing methods of Knowledge Discovery from Data with emphasis on a decision tree model (J48). Results Different dos...
Toxicology Letters, 2014
We report here an in vitro evaluation of silica nanoparticle uptake by lung epithelial cells (A54... more We report here an in vitro evaluation of silica nanoparticle uptake by lung epithelial cells (A549), the cytotoxic effect of the particles and we propose autophagy as possible survival strategy. The effect of surface charge, serum proteins and the influence of inhibitors on the uptake of 20 nm monodispersed nanoparticles with various functional groups are discussed. Uptake rate of the particles with various functional groups is demonstrated to be similar in the presence of serum proteins, while the uptake rate ranking is COOH>NH2>OH under serum free conditions. Our results suggest an actin-dependent, macropinocytotic uptake process that was also confirmed by scanning and transmission electron microscopy. In spite of the intensive active uptake, significant cytotoxic effect is detected only at relatively high concentrations (above 250 μg/mL). Blebbing of the cell surface is observed already at 5h of exposure and is shown to be related to autophagy rather than apoptotic cell death. The A549 cells display elevated levels of autophagosomes, however they do not express typical apoptosis markers such as increased amount of active caspase-3 and release of mitochondrial cytochrome C. Based on these results, we propose here an autophagic activity and cross-talk between autophagic and apoptotic pathways as a mechanism allowing the survival of A549 cells under exposure to silica nanoparticles.
Toxicology Letters, 2010
In this work, we present a complete physicochemical characterization of multi-wall carbon nanotub... more In this work, we present a complete physicochemical characterization of multi-wall carbon nanotubes (mwCNTs) in order to assess their potential toxicological effects in in vitro cell models using Colony Forming Efficiency (CFE) assay. We verified that Dimethyl Sulfoxide (DMSO) was a more suitable solvent to disperse mwCNTs compared to culture medium guaranteeing reproducibility in the preparation of testing dilutions. The CFE assay was carried out on five mammalian cell lines representing the potentially exposed and/or target organs for nanomaterials (lung, liver, kidney, intestine, skin), as well as on mouse fibroblasts cell line, which usually is considered a sensitive model to verify in vitro cytotoxicity of test compounds. A statistically significant toxic effect was found only in human alveolar basal epithelial cells and immortalized mouse fibroblasts, for which the interaction between mwCNTs and cells was additionally studied by Atomic Force and Scanning Electron Microscopy. In this study, we considered and suggested the CFE assay as a promising test for screening studies of cytotoxicity. In addition, combining in vitro tests with physicochemical analysis, this work underlines basic points to be considered when research on nanomaterials has to be carried out, to set up, in our opinion, well-defined and suitable experimental planning and procedures.
Toxicology Letters, 2008
Recent advances in human stem cell biology provide a new opportunity for the development of hepat... more Recent advances in human stem cell biology provide a new opportunity for the development of hepatocyte-like cell lines suitable for use in in vitro toxicity assays. Human embryonic stem cells, by virtue of their combined potential for self-renewal and pluripotency, appear to be particularly useful for the generation of large numbers of cells of specific lineage. Required features of these cells include a fully differentiated phenotype capable of representing in situ hepatocyte functionality, particularly with respect to xenobiotic metabolism and transport. Progress to date demonstrates partial success, but further improvements are still required. Additional challenges include the development of methodologies to enable scaling up, selection and purification, together with extensive validation work to demonstrate the practical utility of the cells for toxicological applications. New areas of research such as direct somatic cell reprogramming have introduced further possibilities for the wider exploitation of stem cell biology in toxicology.
Toxicology, 2010
Stem cell technology combined with emerging surface nano/micro-technologies provides a new tool f... more Stem cell technology combined with emerging surface nano/micro-technologies provides a new tool for better understanding of the mechanisms involved in cell fate decisions and compound-induced adverse reactions. This article provides state-of-the-art on the development of modern multiparameter bio-tests based on interactions between neural stem cells derived from human cord blood and bioengineered surfaces. Cell growth platforms with controlled content, geometry and spatial distribution of bioactive and stem cell attractive areas were fabricated either by micro-contact printing or piezoelectric spotting of polycationic biomolecules or extracellular matrix proteins (ECM) on cell-repellent surfaces. HUCB-NSCs were shown to adhere, differentiate and respond to neurotoxic MeHgCl on functional domains in a manner dependent on protein type and concentration, cell density and serum conditions. While receptor-mediated interactions with ECM proteins under absence of serum promote neuronal differentiation, non-specific adhesion to polycationic molecules maintain cells attached to the surface in non-differentiated stage. Functional domains were further engineered to create "smart" microenvironment by immobilizing to the surface signaling molecules together with ECM proteins. Stimulation of selected intracellular pathways by molecules of Wnt, Shh, CNTF or Notch type resulted in differentiation of HUCB-NSC to either neuronal or astroglial lineage. Sensor techniques applied to HUCB-NSC included measurements of electrical activity using multielectrode array chips. Spontaneous electrical field potentials of HUCB-NSCs were dependent upon developmental stage of tested cells. Bioengineered surfaces, on protein microarrays and micro-electrode array chips provide a novel approach to the multiparameter bio-tests by adding an important information on the sensitivity of certain molecular pathways and functional cellular responses to selected neurotoxins.
Toxicological Sciences, 2011
The toxicological effects of cobalt nanoparticles (Co-NPs) aggregates were examined and compared ... more The toxicological effects of cobalt nanoparticles (Co-NPs) aggregates were examined and compared with those of cobalt ions (Co-ions) using six different cell lines representing lung, liver, kidney, intestine, and the immune system. Dose-response curves were studied in the concentration range of 0.05-1.0mM, employing 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide test, neutral red, and Alamar blue as end point assays following exposures for 48 and 72 h. Data analysis and predictive modeling of the obtained data sets were executed by employing a decision tree model (J48), where training and validation were carried out by an iterative process. It was established, as expected, that concentration is the highest rank parameter. This is because concentration parameter provides the highest information gain with respect to toxicity. The second-rank parameter emerged to be either the compound type (Co-ions or Co-NPs) or the cell model, depending on the concentration range. The third and the lowest rank in the model was exposure duration. The hierarchy of cell sensitivity toward cobalt ions was found to obey the following sequence of cell lines: A549 > MDCK > NCIH441 > Caco-2 > HepG2 > dendritic cells (DCs), with A549 being the most sensitive cell line and primary DCs were the least sensitive ones. However, a different hierarchy pattern emerged for Co-NPs: A549 5 MDCK 5 NCIH441 5 Caco-2 > DCs > HepG2. The overall findings are in line with the hypothesis that the toxic effects of aggregated cobalt NPs are mainly due to cobalt ion dissolution from the aggregated NPs.
Soft Matter, 2009
Microarrays of fibronectin and other extracellular matrix (ECM) proteins were fabricated on plasm... more Microarrays of fibronectin and other extracellular matrix (ECM) proteins were fabricated on plasma-deposited poly(ethyleneoxide) (PEO-like) film coated glass slides to study adhesion of stem cells. The arrays were generated by using a non-contact printing technology. The ...
Sensors and Actuators B: Chemical, 2007
... a Institute for Health and Consumer Protection (IHCP), Joint Research Centre, TP 203, I-21020... more ... a Institute for Health and Consumer Protection (IHCP), Joint Research Centre, TP 203, I-21020 ... acquisition time was kept below 10 min to avoid any possible X-ray induced damage ... For theseexperiments, the different coatings have been deposited on TCPS Petri dishes and a ...
Plasma Processes and Polymers, 2014
This study points out how the plasma modification of PCL porous scaffolds, produced by Solvent Ca... more This study points out how the plasma modification of PCL porous scaffolds, produced by Solvent Casting/Particulate Leaching, may enhance their biocompatibility. A C 2 H 4 /N 2 plasma deposition followed by a H 2 plasma treatment was used to increase the hydrophilicity of the whole scaffold to support osteoblast cell proliferation, both outside and inside the scaffold. A better cell growth was obtained on plasma modified scaffolds.
Plasma Processes and Polymers, 2006
Plasma Processes and Polymers, 2010
Nanotoxicology, 2012
In this work we investigated the toxicological effects of nude and chemically functionalised (-NH... more In this work we investigated the toxicological effects of nude and chemically functionalised (-NH(2), -OH and -COOH groups) multiwall carbon nanotubes (mwCNTs) using immortalised mouse fibroblasts cell line (Balb/3T3) as in vitro model, alternative to the use of animals, to assess basal cytotoxicity, carcinogenic potential, genotoxicity and cell interaction of nanomaterials (NM). Combining in vitro tests such as cell transformation assay and micronucleus with physicochemical and topological analysis, we obtained results showing no cytotoxicity and genotoxicity. Carcinogenic potential and mwCNTs interaction with cells were instead evident. We stressed the importance that different toxicological end points have to be considered when studying NM, therefore, assays able to detect long-term effects, such as carcinogenicity, must be taken into account together with a panel of tests able to detect more immediate effects like basal cytotoxicity or genotoxicity.