Biology subjects

Ioannou, S.

Publications and source records attributed to Ioannou, S..

4 recordsLinked to original sources

bioRxiv2025

Bioengineered bone marrows that can support stem cells and remodel to mimic human disease metabolism and chemotherapeutic effects

Blood cancer drug discovery is reliant on poorly predictive and costly animal models. Therefore, bioengineered, human cell containing, models are attractive to Pharma. Designing effective bone marrow (BM) models is complicated as they need to both regulate haematopoietic stem cell (HSC) phenotype and be able to undergo remodelling to mimic the blood cancer microenvironment. Here, we develop synthetic hybrid niches using poly(ethylacrylate) to organise laminin on hard, bone mimicking, surfaces and interface with soft, marrow mimicking, polyethylene glycol-fibronectin hydrogels. Optimisation of mesenchymal stromal cell (MSC) mechanobiology within the model offers both support for HSCs and remodelling in response to acute myeloid leukaemia derived cells. The remodelling has many parallels to in vivo and patient data including increased dependency on nestin+ve MSCs, enhanced cytoprotection and increased taurine metabolism. We also use the model to demonstrate, as has been seen in vivo, that targeting taurine enhances effects of chemotherapy.

bioengineering↗

bioRxiv2024

Extracellular vesicle bioactivity and potential clinical utility is determined by mesenchymal stromal cell clonal subtype

Mesenchymal stromal cells (MSCs) are a promising source of therapeutic extracellular vesicles (EVs), however it is not clear how heterogeneity within a non-clonal MSC population will affect the collective EV pool. Here we used immortalised clonal MSC lines, termed Y201 and Y202, to examine how MSC phenotype influences EV character and function. Although morphologically similar, Y201 EVs were more abundant in EV biomarkers versus Y202 EVs, with an enhanced miRNA and proteomic content, predicted to contribute to an elaborate EV corona particularly abundant in RGD-containing proteins fibronectin and MFG-E8. We demonstrated that Y201 EVs, but not Y202 EVs, significantly increased the proliferation of articular chondrocytes and that the proliferative effect was mediated at least in part via an RGD (integrin)-FAK-ERK1/2 axis. Both Y201 and Y202 EV subsets significantly reduced proliferative index scores of activated T cells. However, only Y201 EVs, not Y202 EVs, suppressed disease activity compared to controls in different in vivo models of inflammatory peritonitis and arthritis. EVs released by closely related MSC subtypes within the same heterogeneous population differ significantly in terms of cargo abundance, bioactivity, and pre-clinical in vivo efficacy. Analysis of defined EV subsets will aid mechanistic understanding and prioritisation for EV therapeutics.

cell biology↗

bioRxiv2024

High resolution live cell imaging to define ultrastructural and dynamic features of the halotolerant yeast Debaryomyces hansenii

Although some budding yeasts have proved tractable and intensely studied models, others are more recalcitrant. Debaryomyces hansenii, an important yeast species in food and biotechnological industries with curious physiological characteristics, has proved difficult to manipulate genetically and remains poorly defined. To remedy this, we have combined live cell fluorescent dyes with high resolution imaging techniques to define the sub-cellular features of D. hansenii, such as the mitochondria, nuclei, vacuoles and the cell wall. Using these tools, we define biological processes like the cell cycle, organelle inheritance and different membrane trafficking pathways of D. hansenii for the first time. Beyond this, reagents designed to study Saccharomyces cerevisiae proteins were used to access proteomic information about D. hansenii. Finally, we optimised the use of label free holotomography to image yeast, defining the physical parameters and visualising sub-cellular features like membranes and vacuoles. Not only does this work shed light on D. hansenii but this combinatorial approach serves as a template for how other cell biological systems, which are not amenable to standard genetic procedures, can be studied.

cell biology↗

bioRxiv2018

Mapping drinking water and quality of life aspects in urban settings: an application of the urban exposome

Cities face rapid changes leading to increasing inequalities and emerging public health issues that require cost-effective interventions. The urban exposome framework constitutes a novel approach in tackling city-wide challenges, such as those of drinking water quality and quality of life. In this proof-of-concept study, we presented part of the urban exposome of Limassol (Cyprus) focusing on chemical and microbial drinking water quality parameters and their association with urban neighborhood indicators. A perceptions study and an urban population study was conducted. We mapped the water quality parameters and participants opinions on city life (i.e. neighborhood life, health care and green space access) using quarters (small administrative areas) as the reference unit of the city. In an exploratory environment-wide association study analysis, we used all variables (questionnaire responses and water quality metrics) to describe correlations between them accounting, also, for self-reported health status. Overall, urban drinking-water quality using conventional indicators of chemical (disinfection byproducts-trihalomethanes) and microbial (coliforms, E. coli, and Enterococci) quality did not raise particular concerns. The general health and chronic health status of the urban participants were significantly (all >FDR corrected p value of 0.1) associated with different health conditions such as hypertension and asthma, or having financial issues in access to dental care. Additionally, correlations between trihalomethanes and participant characteristics (e.g. household cleaning, drinking water habits) were documented. This proof-of-concept study showed the potential of using integrative approaches to develop urban exposomic profiles and identifying within-city differentiated environmental and health indicators. The characterization of the urban exposome of Limassol will be expanded via the inclusion of biomonitoring tools and untargeted metabolomics platforms.

epidemiology↗