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Research paper thumbnail of The Effect of Uncoated SPIONs on hiPSC-Differentiated Endothelial Cells

International Journal of Molecular Sciences

Background: Endothelial progenitor cells (EPCs) were indicated in vascular repair, angiogenesis o... more Background: Endothelial progenitor cells (EPCs) were indicated in vascular repair, angiogenesis of ischemic organs, and inhibition of formation of initial hyperplasia. Differentiation of endothelial cells (ECs) from human induced pluripotent stem cells (hiPSC)-derived endothelial cells (hiPSC-ECs) provides an unlimited supply for clinical application. Furthermore, magnetic cell labelling offers an effective way of targeting and visualization of hiPSC-ECs and is the next step towards in vivo studies. Methods: ECs were differentiated from hiPSCs and labelled with uncoated superparamagnetic iron-oxide nanoparticles (uSPIONs). uSPION uptake was compared between hiPSC-ECs and mature ECs isolated from patients by software analysis of microscopy pictures after Prussian blue cell staining. The acute and long-term cytotoxic effects of uSPIONs were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay) and Annexin assay. Results: We showed, for the first time, u...

Research paper thumbnail of Brown-Like Adipocyte Progenitors Derived from Human iPS Cells: A New Tool for Anti-obesity Drug Discovery and Cell-Based Therapy?

Handbook of experimental pharmacology, Jan 10, 2018

Alternative strategies are urgently required to fight obesity and associated metabolic disorders ... more Alternative strategies are urgently required to fight obesity and associated metabolic disorders including diabetes and cardiovascular diseases. Brown and brown-like adipocytes (BAs) store fat, but in contrast to white adipocytes, activated BAs are equipped to dissipate energy stored. Therefore, BAs represent promising cell targets to counteract obesity. However, the scarcity of BAs in adults is a major limitation for a BA-based therapy of obesity, and the notion to increase the BA mass by transplanting BA progenitors (BAPs) in obese patients recently emerged. The next challenge is to identify an abundant and reliable source of BAPs. In this chapter, we describe the capacity of human-induced pluripotent stem cells (hiPSCs) to generate BAPs able to differentiate at a high efficiency with no gene transfer. This cell model represents an unlimited source of human BAPs that in a near future may be a suitable tool for both therapeutic transplantation and for the discovery of novel efficie...

Research paper thumbnail of Reprogramming of Adult Peripheral Blood Cells into Human Induced Pluripotent Stem Cells as a Safe and Accessible Source of Endothelial Cells

Stem cells and development, 2018

New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient... more New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient numbers of human endothelial cells (ECs). ECs and their progenitors reside on the interior surface of blood and lymphatic vessels or circulate in peripheral blood; however, their numbers are limited, and they are difficult to expand after isolation. Recent advances in human induced pluripotent stem cell (hiPSC) research have opened possible avenues to generate unlimited numbers of ECs from easily accessible cell sources, such as the peripheral blood. In this study, we reprogrammed peripheral blood mononuclear cells, human umbilical vein endothelial cells (HUVECs), and human saphenous vein endothelial cells (HSVECs) into hiPSCs and differentiated them into ECs. The phenotype profiles, functionality, and genome stability of all hiPSC-derived ECs were assessed and compared with HUVECs and HSVECs. hiPSC-derived ECs resembled their natural EC counterparts, as shown by the expression of the e...

Research paper thumbnail of Vascular network formation in silico using the extended cellular potts model

2016 IEEE International Conference on Image Processing (ICIP), 2016

Research paper thumbnail of N-terminal truncation of microtubule associated protein tau dysregulates its cellular localization

Journal of Alzheimer's disease : JAD, 2015

Tau protein is a member of microtubule-associated protein family. Under pathological conditions, ... more Tau protein is a member of microtubule-associated protein family. Under pathological conditions, tau undergoes multiple modifications that lead to the formation of insoluble deposits in neurons, resulting in neuronal dysfunction in several neurodegenerative disorders collectively called tauopathies, with Alzheimer's disease being the most frequent example. This typical cytosolic protein has been shown to translocate into the nucleus and participate in DNA protection upon stress conditions. In our study, we demonstrate that truncated Tau151-391/4R changes its usual behavior and gains constitutive access into the nucleus of both primary rat neurons and human neuroblastoma cells. Our results show that partial/dysregulated nuclear localization of tau results from the removal of the N-terminal (1-150) residues of the protein. Data obtained by cell fractionation data were supported by confocal microscopy analysis of GFP-fused tau proteins. Furthermore, neither addition of the fusion p...

Research paper thumbnail of The Effect of Uncoated SPIONs on hiPSC-Differentiated Endothelial Cells

International Journal of Molecular Sciences

Background: Endothelial progenitor cells (EPCs) were indicated in vascular repair, angiogenesis o... more Background: Endothelial progenitor cells (EPCs) were indicated in vascular repair, angiogenesis of ischemic organs, and inhibition of formation of initial hyperplasia. Differentiation of endothelial cells (ECs) from human induced pluripotent stem cells (hiPSC)-derived endothelial cells (hiPSC-ECs) provides an unlimited supply for clinical application. Furthermore, magnetic cell labelling offers an effective way of targeting and visualization of hiPSC-ECs and is the next step towards in vivo studies. Methods: ECs were differentiated from hiPSCs and labelled with uncoated superparamagnetic iron-oxide nanoparticles (uSPIONs). uSPION uptake was compared between hiPSC-ECs and mature ECs isolated from patients by software analysis of microscopy pictures after Prussian blue cell staining. The acute and long-term cytotoxic effects of uSPIONs were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay) and Annexin assay. Results: We showed, for the first time, u...

Research paper thumbnail of Brown-Like Adipocyte Progenitors Derived from Human iPS Cells: A New Tool for Anti-obesity Drug Discovery and Cell-Based Therapy?

Handbook of experimental pharmacology, Jan 10, 2018

Alternative strategies are urgently required to fight obesity and associated metabolic disorders ... more Alternative strategies are urgently required to fight obesity and associated metabolic disorders including diabetes and cardiovascular diseases. Brown and brown-like adipocytes (BAs) store fat, but in contrast to white adipocytes, activated BAs are equipped to dissipate energy stored. Therefore, BAs represent promising cell targets to counteract obesity. However, the scarcity of BAs in adults is a major limitation for a BA-based therapy of obesity, and the notion to increase the BA mass by transplanting BA progenitors (BAPs) in obese patients recently emerged. The next challenge is to identify an abundant and reliable source of BAPs. In this chapter, we describe the capacity of human-induced pluripotent stem cells (hiPSCs) to generate BAPs able to differentiate at a high efficiency with no gene transfer. This cell model represents an unlimited source of human BAPs that in a near future may be a suitable tool for both therapeutic transplantation and for the discovery of novel efficie...

Research paper thumbnail of Reprogramming of Adult Peripheral Blood Cells into Human Induced Pluripotent Stem Cells as a Safe and Accessible Source of Endothelial Cells

Stem cells and development, 2018

New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient... more New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient numbers of human endothelial cells (ECs). ECs and their progenitors reside on the interior surface of blood and lymphatic vessels or circulate in peripheral blood; however, their numbers are limited, and they are difficult to expand after isolation. Recent advances in human induced pluripotent stem cell (hiPSC) research have opened possible avenues to generate unlimited numbers of ECs from easily accessible cell sources, such as the peripheral blood. In this study, we reprogrammed peripheral blood mononuclear cells, human umbilical vein endothelial cells (HUVECs), and human saphenous vein endothelial cells (HSVECs) into hiPSCs and differentiated them into ECs. The phenotype profiles, functionality, and genome stability of all hiPSC-derived ECs were assessed and compared with HUVECs and HSVECs. hiPSC-derived ECs resembled their natural EC counterparts, as shown by the expression of the e...

Research paper thumbnail of Vascular network formation in silico using the extended cellular potts model

2016 IEEE International Conference on Image Processing (ICIP), 2016

Research paper thumbnail of N-terminal truncation of microtubule associated protein tau dysregulates its cellular localization

Journal of Alzheimer's disease : JAD, 2015

Tau protein is a member of microtubule-associated protein family. Under pathological conditions, ... more Tau protein is a member of microtubule-associated protein family. Under pathological conditions, tau undergoes multiple modifications that lead to the formation of insoluble deposits in neurons, resulting in neuronal dysfunction in several neurodegenerative disorders collectively called tauopathies, with Alzheimer's disease being the most frequent example. This typical cytosolic protein has been shown to translocate into the nucleus and participate in DNA protection upon stress conditions. In our study, we demonstrate that truncated Tau151-391/4R changes its usual behavior and gains constitutive access into the nucleus of both primary rat neurons and human neuroblastoma cells. Our results show that partial/dysregulated nuclear localization of tau results from the removal of the N-terminal (1-150) residues of the protein. Data obtained by cell fractionation data were supported by confocal microscopy analysis of GFP-fused tau proteins. Furthermore, neither addition of the fusion p...