Biology subjects

Fomina, A.

Publications and source records attributed to Fomina, A..

4 recordsLinked to original sources

bioRxiv2025

Novel hyperplastic expansion of white adipose tissue underlies the metabolically healthy obese phenotype of male LFABP null mice

Obesity is an important risk factor for the development of metabolic syndrome disorders. We previously showed that the liver fatty acid-binding protein null mouse (LFABP-/-) becomes obese upon high-fat diet (HFD) feeding but remains metabolically healthy. Here we find that the obese LFABP-/- mouse increases subcutaneous adipose tissue (SAT) mass by markedly increasing the number rather than the size of adipocytes, as is typical with HFD. Indeed, while HFD-fed LFABP-/- mice had almost double the fat mass of WT, SAT adipocyte size was >4-fold smaller and adipocyte number was 5-fold higher in the LFABP-/-. Transcriptomic analysis of SAT revealed that Lfabp deletion alters the expression of multiple pathways that modulate adipose expansion and function including cholesterol biosynthesis, adipogenesis, and extracellular matrix remodeling. LFABP is expressed in liver and small intestine but not in adipose tissues, thus its ablation may promote interorgan crosstalk that drives hyperplastic expansion of metabolically beneficial SAT, contributing to the healthy obese phenotype of the LFABP-/- mouse.

cell biology↗

bioRxiv2025

In-House Manufacturing of 3D Culture Chips via Vacuum Thermoforming for Enhanced Imaging Applications

Engineered 3D in vitro cancer models, particularly those that facilitate image-based readouts capable of distinguishing the behavior of different cell populations, have become crucial tools in the discovery process. One such model, 96-GLAnCE (Gels for Live Analysis of Compartmentalized Environments), allows for longitudinal imaging of tumor cell dynamics and therapy response. However, the widespread adoption of 96-GLAnCE has been limited by the need for expensive, specialized fabrication equipment. To overcome this challenge, we have optimized a desktop vacuum thermoforming technique for the in-house production of 96- GLAnCE bottom chips using thin polystyrene films. This optimization has led to the reliable and consistent fabrication of devices. Notably, using thin polystyrene films reduces the overall thickness of the chips, enabling high-magnification imaging for studying primary tumor cell phenotypes in 3D with single-cell and subcellular resolution. Our thermoformed devices offer a flexible, cost-effective solution for addressing a wide range of biological questions across various time scales.

bioengineering↗

bioRxiv2024

Reversible and reusable compartmentalized microfluidic chip for coculture of dorsal root ganglion neurons

Compartmentalized microfluidic chips play an important role in understanding the cellular mechanisms involved in neurodegenerative disorders. Dorsal root ganglia are a well-established model for modelling the peripheral nervous system (PNS), but their development on a chip remains limited. Furthermore, it would be beneficial for the devices to be openable in order to access the biological material inside for analyses. Easy to prototype and biocompatible, styrenic block copolymers (SBC) are an alternative to polydimethylsiloxane (PDMS) that offer both reversible and permanent bonding properties. This paper presents a fast and straightforward method to produce compartmentalized SBC chips. The study validates the culture of murine dorsal root ganglia explants, comparing it to the standard methods, to obtain a model of the PNS. Moreover, the reversible bonding properties of the SBC permit the reuse of the chip with a quick and easy cleaning protocol. It provides direct access to the cells, opening the way for imaging and molecular biology analysis. The comparison of the resources required to produce PDMS and SBC chips highlights the importance of moving to reusable devices. These detachable, easy-to-manufacture and sustainable all-thermoplastic platforms provide an alternative way of prototyping compartmentalized devices for in vitro PNS modeling.

biophysics↗

bioRxiv2023

An Engineered 3D Co-culture Model of Primary Macrophages and Patient-Derived Tumour Cells to Explore Cellular Responses in the Graded Hypoxic Microenvironment of Pancreatic Cancer

In pancreatic ductal adenocarcinoma (PDAC), tumour associated macrophages (TAMs) are a heterogeneous immune cell population that interact with cancer cells to promote malignancy, chemo-resistance, and immunosuppression. Aside from TAMs, hypoxia is a prominent feature of PDAC that can rewire cells to survive and enhance malignancy in the tumour microenvironment (TME). Deciphering the interactions between macrophages, cancer cells and hypoxia could lead to the development of effective immune-targeted therapies for PDAC. However, there are only a few models that physiologically recapitulate the PDAC TME and allow for meaningful interrogation of cancer-immune cell interactions in hypoxia. Here, we develop a model of primary macrophages and PDAC patient organoid-derived cells by adapting TRACER, a paper-based, engineered 3D model that allows snapshot analysis of cellular response in hypoxia. In this study, we establish a direct co-culture method of primary macrophages and PDAC organoid cells in TRACER and demonstrate that TRACER co-cultures generate hypoxic gradients and show expected phenotypic responses to this hypoxic gradient. Moreover, we report for the first time in a human in vitro model that hypoxic macrophages exert a graded chemoprotective effect on gemcitabine-treated PDAC organoid cells, and that interactions between cancer cells and macrophages from the inner layers of TRACER indirectly attenuate the inflammatory response of donor-derived T-cells. Overall, the TRACER co-culture system is a novel, fully human 3D in vitro cancer-immune model for evaluating the response of macrophages and cancer cells in a hypoxic gradient.

bioengineering↗