Biology subjects

Modena, M. M.

Publications and source records attributed to Modena, M. M..

4 recordsLinked to original sources

bioRxiv2026

Microfluidic System for On-Demand Imaging of Organotypic Slices

Organotypic brain slice cultures (OSCs) provide a physiologically relevant model for recapitulating complex tissues in vitro. However, the longitudinal monitoring of dynamic processes in OSCs through high-resolution imaging is limited in standard culturing methods, as they rely on slice placement on porous membranes at the air-liquid interface to preserve tissue viability. Here, a new experimental paradigm based on a modular slice culture insert is introduced, which is compatible with static and perfused culturing, and facilitates longitudinal observation of cellular and tissue dynamics at high spatiotemporal resolution. Besides compatibility with conventional culturing in well plates, the insert is integrated into an automated microfluidic instrument to provide user-friendly operation while enabling precise temporal fluid control and compound delivery. The system is applied to monitor calcium responses and cellular morphology of virally labeled cerebellar astrocytes and Purkinje cells exposed to different concentrations of glutamate. Cellular responses were evaluated at baseline, during glutamate exposure, and 48 h and 96 h after stimulation to identify acute and long-term excitotoxic effects. Our results indicate that the developed system enables high-resolution monitoring of cellular morphology and dynamic events of the same intact tissue over multiple days, which provides a robust foundation for mechanistic investigations of neural signaling.

bioengineering↗

bioRxiv2025

Real-Time Tracking of Tumor Invasion Dynamics in Organotypic Brain Slices at Subcellular Resolution

Replicating the cytoarchitecture and cell heterogeneity of the brain in vitro remains challenging. Although ex vivo organotypic slices preserve native tissue complexity, current culturing methods limit long-term, high-resolution imaging and restrict temporally controlled perturbations. Here, we present PHIROS, a microfluidic platform for high-resolution imaging of organotypic slices that supports static culturing of excised tissue at the air-liquid interface and provides continuous optical access for extended imaging at subcellular resolution. Controlled perfusion with oxygenated medium preserves tissue viability over several days, enabling, e.g., the monitoring of spontaneous and pharmacologically modulated astrocytic calcium activity. Using PHIROS we characterized medulloblastoma (MB) cell behavior in a physiological tumor microenvironment and observed dynamic F-actin-driven interactions with tissue-resident astrocytes, as well as leading edge localization of the immune-checkpoint marker B7-H3 in invading tumor cells. Quantitative assessment of mitochondria transfer across heterotypic actin-rich connections evidences the potential of PHIROS as a versatile system for mechanistic studies in a tissue context, enabling controlled compound exposure and high-resolution imaging in physiologically relevant tissue settings.

bioengineering↗

bioRxiv2022

3D in vitro blood-brain-barrier model for investigating barrier insults

The blood-brain-barrier (BBB) prevents that harmful substances in the blood enter the brain, and barrier disruption has been associated with a variety of central-nervous-system diseases. In vitro BBB models enable to recapitulate the BBB behavior in a controlled environment to investigate how the barrier reacts to stress events and external insults. Here, we present a human-cell-based BBB platform with integrated, transparent electrodes to monitor barrier tightness in real time at high spatiotemporal resolution. The BBB model includes human cerebral endothelial cells and primary human pericytes and astrocytes in a three-dimensional arrangement within a pump-free, open microfluidic platform. With our platform, we demonstrate that oxygen-glucose deprivation (OGD), which mimics the characteristics of an ischemic insult, induces a rapid remodeling of the cellular actin structures and subsequent morphological changes in the endothelial cells. High-resolution live imaging showed the formation of large actin stress-fiber bundles in the endothelial layer during OGD application, which ultimately led to cell shrinkage and barrier breakage. Simultaneous electrical measurements showed a rapid decrease of the barrier electrical resistance before the appearance of the stress fibers, which indicates that the barrier function is compromised already before the appearance of drastic morphological changes. The results demonstrate that our BBB platform recapitulates the main barrier functions in vitro and can be used to investigate the rapid reorganization of the BBB upon application of external stimuli.

bioengineering↗

bioRxiv2022

Microphysiological Drug-Testing Platform For Identifying Responses To Prodrug Treatment In Primary Leukemia

Despite increasing survival rates of pediatric leukemia patients over the past decades, the outcome of some leukemia subtypes has remained dismal. Drug sensitivity and resistance testing on patient-derived leukemia samples provide important information to tailor treatments for high-risk patients. However, currently used well-based drug screening platforms have imitations in predicting the effects of prodrugs, a class of therapeutics that require metabolic activation to become effective. To address this issue, we developed a microphysiological drug-testing platform that enables co-culturing of patient-derived leukemia cells, human bone marrow mesenchymal stromal cells, and human liver microtissues within the same microfluidic platform. This platform also enables to control the physical interaction between the diverse cell types. We were able to recapitulate hepatic prodrug activation of ifosfamide in our platform, which is very difficult in traditional well-based assays. By testing the susceptibility of primary patient-derived leukemia samples to the prodrug ifosfamide, we identified sample-specific sensitivities to ifosfamide in primary leukemia samples. We found that our microfluidic platform enabled the recapitulation of physiologically relevant conditions and the testing of prodrugs including short-lived and unstable metabolites. The platform holds great potential for clinical translation and precision chemotherapy selection.

bioengineering↗