Periodic Reporting for period 2 - PLAST_CELL (A multiplexed biomimetic imaging platform for assessing single cell plasticity (Plastomics) and scoring of tumour malignancy)
Reporting period: 2023-05-01 to 2024-10-31
Metastasis, , the spread of primary tumor cells to distant organs, accounts for over 90% of cancer-related deaths and remains a significant clinical challenge due to limited treatment options. Metastatic cells adapt to hostile environments through changes in cell states and dynamic behaviors, such as alterations in cell shape, migration, and proliferation. This adaptation ability, also termed cellular plasticity, is a hallmark of metastasis and has been suggested to play a role in therapy resistance and cancer aggressiveness. However, it is poorly defined, and current clinical methods cannot analyze plasticity at the single-cell level or provide functional insights into adaptive behaviors.
The PLAST_CELL project aims to bridge this gap by creating a cutting-edge platform that integrates biomimetic 3D microenvironments, high-resolution live-cell imaging, and computational analysis. This platform enables real-time, single-cell assessment of cancer cell adaptations, quantitatively measuring tumor plasticity and aggressiveness. The ultimate objective is to develop PLAST_SCORE, a scoring model to predict tumor behavior and enhance clinical decision-making.
The technology and insights from PLAST_CELL will address long-standing challenges in biomedicine, offering a transformative leap for evaluating cancer cells and patient samples. Outputs will also support the development of advanced imaging, microfluidics, and bioinformatics tools applicable to normal and pathological processes.
The PLAST_CELL project aims to bridge this gap by creating a cutting-edge platform that integrates biomimetic 3D microenvironments, high-resolution live-cell imaging, and computational analysis. This platform enables real-time, single-cell assessment of cancer cell adaptations, quantitatively measuring tumor plasticity and aggressiveness. The ultimate objective is to develop PLAST_SCORE, a scoring model to predict tumor behavior and enhance clinical decision-making.
The technology and insights from PLAST_CELL will address long-standing challenges in biomedicine, offering a transformative leap for evaluating cancer cells and patient samples. Outputs will also support the development of advanced imaging, microfluidics, and bioinformatics tools applicable to normal and pathological processes.
During the second reporting period, the project achieved several key milestones:
- Technological Innovations: A contact-free micro-confinement system was developed, resolving technical and industrial limitations of traditional PDMS-based systems. This advancement enhances scalability and reproducibility for clinical and industrial applications. Additionally, the imaging system was upgraded to include high-speed structured illumination microscopy (SIM), enabling detailed visualization of cytoskeletal dynamics in confined live cells.
- Computational Advancements: A computational pipeline for morphodynamic analysis was established to extract quantitative descriptors of cell morphology and behavior. This pipeline is currently analyzing extensive datasets from murine and human cancer cell lines, revealing correlations between morphological traits and tumor aggressiveness, crucial for PLAST_SCORE development.
- Clinical Relevance: A consistent data set of mouse breast cancer cell lines of known aggressiveness, subsequently used for the computation pipeline, was generated. In addition, we started testing to culture patient-derived organoids (PDOs) from breast cancer patients to later analyze them both in vivo and in vitro to generate clinically relevant data to validate the PLAST_CELL platform. In the meanwhile, we are employing patient-derived xenogaph (PDX) models that have already been validated in vivo.
- Dissemination and Exploitation: Dissemination activities include a dynamic online presence and collaboration with academic, clinical, and industrial stakeholders. A patent was filed for the novel confinement technology, positioning the project for future commercialization.
The cross-disciplinary PLAST_CELL consortium combines expertise in cell and tissue dynamics, cancer metastasis, advanced bioimaging, and computational biology, alongside industrial R&D capabilities.
- Technological Innovations: A contact-free micro-confinement system was developed, resolving technical and industrial limitations of traditional PDMS-based systems. This advancement enhances scalability and reproducibility for clinical and industrial applications. Additionally, the imaging system was upgraded to include high-speed structured illumination microscopy (SIM), enabling detailed visualization of cytoskeletal dynamics in confined live cells.
- Computational Advancements: A computational pipeline for morphodynamic analysis was established to extract quantitative descriptors of cell morphology and behavior. This pipeline is currently analyzing extensive datasets from murine and human cancer cell lines, revealing correlations between morphological traits and tumor aggressiveness, crucial for PLAST_SCORE development.
- Clinical Relevance: A consistent data set of mouse breast cancer cell lines of known aggressiveness, subsequently used for the computation pipeline, was generated. In addition, we started testing to culture patient-derived organoids (PDOs) from breast cancer patients to later analyze them both in vivo and in vitro to generate clinically relevant data to validate the PLAST_CELL platform. In the meanwhile, we are employing patient-derived xenogaph (PDX) models that have already been validated in vivo.
- Dissemination and Exploitation: Dissemination activities include a dynamic online presence and collaboration with academic, clinical, and industrial stakeholders. A patent was filed for the novel confinement technology, positioning the project for future commercialization.
The cross-disciplinary PLAST_CELL consortium combines expertise in cell and tissue dynamics, cancer metastasis, advanced bioimaging, and computational biology, alongside industrial R&D capabilities.
The PLAST_CELL project aspires to transform oncology diagnostics and therapy by:
- Standardizing Cellular Plasticity Assessment: Establishing a platform for evaluating cellular plasticity to improve clinical decision-making and personalized treatment strategies.
- Pioneering "Plastomics": Integrating quantitative cell biology and computational analysis to uncover the dynamics of tumor plasticity.
PLAST_CELL will produce globally accessible datasets, enabling high-quality standardized analyses for novel biological discoveries. These datasets will reduce reliance on animal models and support selective drug screening and clinically relevant database creation, advancing personalized medicine and reinforcing Europe’s leadership in global health initiatives.
Technological outputs from the project will contribute to advancements in imaging, microfluidics, and computational biology, extending applications to regenerative medicine and developmental biology. By commercializing the technology, the project will generate revenue for further research, create market opportunities, and foster employment, benefiting society as a whole.
By project completion, PLAST_CELL aims to establish an integrated framework combining biomimetic environments, high-resolution imaging, and advanced data analytics, setting new standards in cancer research and personalized medicine.
- Standardizing Cellular Plasticity Assessment: Establishing a platform for evaluating cellular plasticity to improve clinical decision-making and personalized treatment strategies.
- Pioneering "Plastomics": Integrating quantitative cell biology and computational analysis to uncover the dynamics of tumor plasticity.
PLAST_CELL will produce globally accessible datasets, enabling high-quality standardized analyses for novel biological discoveries. These datasets will reduce reliance on animal models and support selective drug screening and clinically relevant database creation, advancing personalized medicine and reinforcing Europe’s leadership in global health initiatives.
Technological outputs from the project will contribute to advancements in imaging, microfluidics, and computational biology, extending applications to regenerative medicine and developmental biology. By commercializing the technology, the project will generate revenue for further research, create market opportunities, and foster employment, benefiting society as a whole.
By project completion, PLAST_CELL aims to establish an integrated framework combining biomimetic environments, high-resolution imaging, and advanced data analytics, setting new standards in cancer research and personalized medicine.