Publications by authors named "Ilona Szabłowska-Gadomska"

8 Publications

  • Page 1 of 1

Peritoneal fluid stimulates neoplastic transformation of normal HEK 293 cells by high expression of pluripotent genes.

Pol J Pathol 2018;69(3):399-310

Gynecological cancers constitute a serious problem in the world. Their advanced stages are often characterized by the accumulation of ascites, which leads to spreading of cancer cells outside their primary focus. Despite progress in the treatment, prognoses are still not satisfactory. The main causes of these failures are chemoresistance, metastases and recurrences of the disease, which is influenced by, among others, the microenvironment of cancer cells. This study investigated the effect of the microenvironment, which create ascites derived from patients with ovarian and endometrial cancer to non-gynecological HEK 293 cells. The effect of the gynecological cancer microenvironment on HEK 293 cells behaviour was analysed using RT-PCR, qRT-PCR, Western blotting and functional analysis (invasion assays, hanging drop) methods. Our results suggest that the key genes for the development of cancer can be regulated by epigenetic and hypoxia-inducible factor in dependent manner. It was observed that in vitro microenvironment, which is created by cells originating from patients with gynecological cancer (ovarian cancer, endometrial cancer) is able to generate changes in HEK 293 cells by itself.
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http://dx.doi.org/10.5114/pjp.2018.79550DOI Listing
May 2019

Epigenetic Modulation of Stem Cells in Neurodevelopment: The Role of Methylation and Acetylation.

Front Cell Neurosci 2017 7;11:23. Epub 2017 Feb 7.

Stem Cell Bioengineering Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences Warsaw, Poland.

The coordinated development of the nervous system requires fidelity in the expression of specific genes determining the different neural cell phenotypes. Stem cell fate decisions during neurodevelopment are strictly correlated with their epigenetic status. The epigenetic regulatory processes, such as DNA methylation and histone modifications discussed in this review article, may impact both neural stem cell (NSC) self-renewal and differentiation and thus play an important role in neurodevelopment. At the same time, stem cell decisions regarding fate commitment and differentiation are highly dependent on the temporospatial expression of specific genes contingent on the developmental stage of the nervous system. An interplay between the above, as well as basic cell processes, such as transcription regulation, DNA replication, cell cycle regulation and DNA repair therefore determine the accuracy and function of neuronal connections. This may significantly impact embryonic health and development as well as cognitive processes such as neuroplasticity and memory formation later in the adult.
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http://dx.doi.org/10.3389/fncel.2017.00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293809PMC
February 2017

Antibacterial Activity and Cytotoxicity of Silver(I) Complexes of Pyridine and (Benz)Imidazole Derivatives. X-ray Crystal Structure of [Ag(2,6-di(CH2OH)py)2]NO3.

Molecules 2016 Jan 28;21(2):87. Epub 2016 Jan 28.

Department of Bioinorganic Chemistry, Medical University of Lodz, Muszyńskiego 1, 90-151 Łódź, Poland.

Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922 and Proteus hauseri ATCC 13315. The results were compared with those of silver nitrate, a silver sulfadiazine drug and appropriate ligands. The most significant antibacterial properties were exerted by silver(I) complexes containing benzimidazole derivatives. The cytotoxic activity of the complexes was examined against B16 (murine melanoma) and 10T1/2 (murine fibroblasts) cells. All of the tested silver(I) compounds were not toxic to fibroblast cells in concentration inhibited cancer cell (B16) viability by 50%, which ranged between 2.44-28.65 µM. The molecular and crystal structure of silver(I) complex of 2,6-di(hydroxymethyl)pyridine was determined by single-crystal X-ray diffraction analysis. The most important features of the crystal packing and intermolecular non-covalent interactions in the Ag(I) complex were quantified via Hirshfeld surface analysis.
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http://dx.doi.org/10.3390/molecules21020087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274122PMC
January 2016

Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner.

Cytotherapy 2014 Jul 13;16(7):881-92. Epub 2014 Apr 13.

NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. Electronic address:

Background Aims: As we approach the era of mesenchymal stem cell (MSC) application in the medical clinic, the standarization of their culture conditions are of the particular importance. We re-evaluated the influences of oxygens concentration on proliferation, stemness and differentiation of human umbilical cord Wharton Jelly-derived MSCs (WJ-MSCs).

Methods: Primary cultures growing in 21% oxygen were either transferred into 5% O2 or continued to grow under standard 21% oxygen conditions. Cell expansion was estimated by WST1/enzyme-linked immunosorbent assay or cell counting. After 2 or 4 weeks of culture, cell phenotypes were evaluated using microscopic, immunocytochemical, fluorescence-activated cell-sorting and molecular methods. Genes and proteins typical of mesenchymal cells, committed neural cells or more primitive stem/progenitors (Oct4A, Nanog, Rex1, Sox2) and hypoxia inducible factor (HIF)-1α-3α were evaluated.

Results: Lowering O2 concentration from 21% to the physiologically relevant 5% level substantially affected cell characteristics, with induction of stemness-related-transcription-factor and stimulation of cell proliferative capacity, with increased colony-forming unit fibroblasts (CFU-F) centers exerting OCT4A, NANOG and HIF-1α and HIF-2α immunoreactivity. Moreover, the spontaneous and time-dependent ability of WJ-MSCs to differentiate into neural lineage under 21% O2 culture was blocked in the reduced oxygen condition. Importantly, treatment with trichostatin A (TSA, a histone deacetylase inhibitor) suppressed HIF-1α and HIF-2α expression, in addition to blockading the cellular effects of reduced oxygen concentration.

Conclusions: A physiologically relevant microenvironment of 5% O2 rejuvenates WJ-MSC culture toward less-differentiated, more primitive and faster-growing phenotypes with involvement of HIF-1α and HIF-2α-mediated and TSA-sensitive chromatin modification mechanisms. These observations add to the understanding of MSC responses to defined culture conditions, which is the most critical issue for adult stem cells translational applications.
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http://dx.doi.org/10.1016/j.jcyt.2014.02.009DOI Listing
July 2014

Induced pluripotent stem cells (iPSc) for gene therapy.

Med Wieku Rozwoj 2013 Jul-Sep;17(3):191-5

Department of Applied Pharmacy and Bioengineering, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland, 0048 572-09-65,

The generation of autologous pluripotent stem cells by reprogramming and then their differentiation into any cell type is a very attractive prospect for biomedicine. Additionally, if it were possible to repair malfunctioning genes it would mean that there is hope for patients suffering from incurable diseases in which conventional treatment does not give satisfactory results. Data from animal models are promising. But there are still issues that must be solved, such as the low efficiency of the derivation of induced pluripotent cells, and most importantly, making sure that the techniques used both for reprogramming cells, as well as for gene therapy are safe.
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January 2014

Epigenetic and molecular signature of human umbilical cord blood-derived neural stem cell (HUCB-NSC) neuronal differentiation.

Acta Neurobiol Exp (Wars) 2013 ;73(1):143-56

NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

In the context of cell therapy, the epigenetic status of core stemness transcription factor (STF) genes regulating the cell proliferation/differentiation program is of primary interest. Our results confirmed that in vitro differentiation of the umbilicalcord-blood-derived-neural-stem-cells (HUCB-NSC) coincides with the progressive down-regulation of Oct3/4 and Nanog gene expression. Consistently and in parallel with the repression of gene transcription, a substantial increase in the mosaic cytosine methylation CpG dinucleotide was observed in the promoter regions of these STF genes. However none of the histone-H3 post-translational-modifications (PTM) known to be associated with transcriptionally active genes (H3Ac and H3K4me3) or repressed genes (H3K9me3 and H3K27me3) seemed to vary in relation to the progression of cell differentiation and down-regulation of STF genes. This indicates an uncoupling between STF gene expression and above mentioned histone PTMs. In contrast, the overall methylation of nuclear chromatin at repressive histone H3K9me3 was significantly higher than H3K4 trimetylation in expanding HUCB-NSC cultures and then increases through the progression of cell differentiation. These observations suggest different epigenetic programs of gene repression realized in the cell nuclei of differentiating HUCB-NSC cultures with uneven involvement of the repressive histone PTMs.
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December 2013

Treatment with small molecules is an important milestone towards the induction of pluripotency in neural stem cells derived from human cord blood.

Acta Neurobiol Exp (Wars) 2012 ;72(4):337-50

NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

Standardization of methods for obtaining iPS cells from the human somatic cells and then their successful differentiation are important in the context of their possible application in personalized cell therapy and the development of toxicological and pharmacological tests. In the present study, the influence of the small molecules representing epigenetic modulators (histone deacetylase inhibitor Trichostatin A and DNA methyltransferase inhibitor RG-108) on the process of reverting neural progenitors from HUCB-NSC (Human Umbilical Cord Blood Neural Stem Cell) line to the pluripotent state was tested. The experiments were conducted in low oxygen tension, in three different experimental layouts: (1) in the presence of reprogramming/recombinant polyarginine-tailed proteins; (2) with recombinant proteins and small molecules; (3) only in the presence of small molecules. We wanted to find out, whether it will be possible to induce pluripotent state of neural stem cells only by epigenetic modulators. Our results revealed that the inhibitors of DNA methylation and histone deacetylation used along with 5 percent oxygen tension can only transiently induce or elevate some pluripotency genes in neural progenitors with different pattern, but were not sufficient for stable reprogramming. The iPS cells from neural progenitor cells of HUCBNSC were obtained only when TSA, RG-108 and reprogramming proteins have been applied simultaneously. These cells were tested for the expression of the selected pluripotency genes and in functional assays to prove their pluripotency stage. The obtained data show that the small molecules in conjunction with reprogramming factors are the potent tools in cell reprogramming.
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November 2013

Influence of low oxygen tensions on expression of pluripotency genes in stem cells.

Acta Neurobiol Exp (Wars) 2011 ;71(1):86-93

NeuroRepair Department, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

The stem cells are characterized by self-renewal ability and potential to differentiate into other cell types of the body. They are residuing in defined microenvironments - "stem cell niches". The embryonic stem cells (ESC) are derived from embryos which exist in 3-5 percent oxygen condition. This environment is physiologically normal not only for ES cells but also for many other types of stem cells including neural stem cells (NSC). These observations suggest that low oxygen condition plays a very important role in the maintenance of cell stemness. Pluripotency is regulated by the family of hypoxia inducible factors (HIFs), which are dependent on oxygen tensions. HIF-2α is an upstream regulator of Oct4, which is one of the main transcription factors used to generate the first induced pluripotent stem cells (iPSCs). It has been shown that knock-down of HIF-2α but not HIF-1α, leads to a decrease in the expression of Oct4, Nanog and Sox2, which are important stem cells markers. The structure of hypoxia inducible factors as well as their behavior in hypoxia and normoxia was described. Therefore optimization of oxygen concentration seems to be crucial from the stem cell transplantation as well as iPS transplantation standpoint. Although many experiments with cell culture under low oxygen condition were performed, there is still much that is unknown. This short review presents some aspects on important issue of hypoxia induced regulation of stemness.
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August 2011