Jana Petr


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Last Name

Petr

First Name

Jana

Organisational unit

03684 - Hierlemann, Andreas / Hierlemann, Andreas

Search Results

Publications 1 - 8 of 8
  • Yan, Shen; Ciraulo, Bernard; Jovanovic, Dejana; et al. (2024)
    BTM 2024 - Booklet
  • Petr, Jana; Lin, Meng-Syuan; Hierlemann, Andreas; et al. (2024)
  • Girardin, Sophie; Clément, Blandine; Ihle, Stephan J.; et al. (2022)
    Lab on a Chip
    Bottom-up neuroscience, which consists of building and studying controlled networks of neurons in vitro, is a promising method to investigate information processing at the neuronal level. However, in vitro studies tend to use cells of animal origin rather than human neurons, leading to conclusions that might not be generalizable to humans and limiting the possibilities for relevant studies on neurological disorders. Here we present a method to build arrays of topologically controlled circuits of human induced pluripotent stem cell (iPSC)-derived neurons. The circuits consist of 4 to 50 neurons with well-defined connections, confined by microfabricated polydimethylsiloxane (PDMS) membranes. Such circuits were characterized using optical imaging and microelectrode arrays (MEAs), suggesting the formation of functional connections between the neurons of a circuit. Electrophysiology recordings were performed on circuits of human iPSC-derived neurons for at least 4.5 months. We believe that the capacity to build small and controlled circuits of human iPSC-derived neurons holds great promise to better understand the fundamental principles of information processing and storing in the brain.
  • Petr, Jana; Lin, Meng-Syuan; Machado Almeida, Pedro; et al. (2023)
    ALTEX Proceedings ~ Abstracts of the 2nd Microphysiological Systems World Summit
  • Petr, Jana; Vivancos Stalin, Lucie; Baumgartner, Matthias; et al. (2022)
  • Lin, M.-S.; Petr, Jana; Hochuli, D.; et al. (2023)
  • Petr, Jana; Lin, Meng-Syuan; Hierlemann, Andreas; et al. (2024)
    ALTEX Proceedings ~ MPS World Summit 2024
  • Petr, Jana (2025)
    Understanding disease mechanisms requires models that accurately reflect the complexity of human tissues and organs. Tissues are composed of multiple, specialized cell types arranged in a structured architecture. However, most experimental studies rely on isolated cells cultured on non-physiological plastic substrates. Advanced 3D culture systems and self-organized tissue models, e.g. “organ-on-chip” microfluidic systems and organoids, feature greatly improved physiological relevance. Nevertheless, in vitro replication of the intricate organization of specific tissues, such as the cerebellum or the liver, remains a significant challenge. Tissue slices offer a promising alternative, as they preserve ex vivo the cellular heterogeneity, spatial arrangement and native signaling pathways of the tissue of origin. However, their use for studies of dynamic biological processes is often limited by technical constraints and by the restricted access for high-resolution imaging. To address these limitations, this thesis presents three microfluidic platforms custom-designed for ex vivo slice culturing and high-resolution imaging. All systems support tissue slice viability over extended periods, owing to an optimized perfusion with oxygenated medium, which largely compensates for the loss of an active supply through tissue vasculature upon tissue excision. The developed platforms were fabricated from inert plastics, which enables their use for investigating the effects of small-molecule exposure. Each platform was developed with distinct design features to accommodate different experimental needs and tissue types: (i) A dynamic platform enabling the static culturing of organotypic brain tissue slices at the air-liquid interface. Thereafter, the platform is sealed and perfused to allow for continuous, high-resolution imaging. The platform was used to study medulloblastoma invasion into cerebellar slices and tumor–astrocyte interactions over several days, highlighting the importance of a preserved tumor microenvironment for understanding disease progression. (ii) A tissue-culturing platform that could be integrated into a commercial, automated fluidic system for (i) time-controlled exposure to soluble factors (i.e., drugs) and for (ii) longitudinal studies including on-demand imaging over multiple days. The platform allows for alternating between perfusion imaging sessions and maintenance culturing at the air-liquid interface in a standard incubator. We employed the platform to investigate disruptions in glutamate homeostasis in cerebellar astrocytes and Purkinje cells by means of calcium imaging. (iii) A microfluidic system for perfusion-based culturing of precision-cut tissue slices embedded in a hydrogel matrix. In proof-of-concept experiments, the system was utilized to culture human liver slices more than 72 hours ex vivo, demonstrating improved hepatocyte morphology and cell survival under oxygenated perfusion compared to static culture methods. Collectively, the developed platforms support tissue slice viability ex vivo and provide long-term optical access, which enables to study dynamic cellular processes in a physiologically relevant context. The modular design and compatibility with standard high-resolution microscopes render the platforms powerful tools for disease modeling and personalized medicine, as primary patient material can be used.
Publications 1 - 8 of 8