The global aim of this project is to imitate and characterize the heterogeneity of immuno-stromal microenvironment in pancreatic ductal adenocarcinoma (PDAC) and explore its implications for diagnostics and innovative therapies. The project focuses on developing expandable pancreatic progenitor cell (ePPC) lines with acinar lineage potential derived from human embryonic stem cells (hESCs). These lines will serve as a platform for studying early tumorigenic processes.
The subsequent objective is to develop a 3D co-culture system integrating ePPC-derived organoids with stromal fibroblasts and immune cells. These models will enable the detailed investigation of early immuno-stromal signaling events critical to tumor initiation, including stromal activation, immune suppression, and epithelial responses. Emphasizing early microenvironmental changes is essential, as current models often begin with fully developed tumor cells, leaving a significant gap in understanding early tumor initiation and cellular responses. By growing 3D cellular models within extracellular matrices like Matrigel together with stromal and immune cells, we can replicate tumor architecture and conduct in-depth investigations of the PDAC microenvironment to unravel molecular machinery involved in stromal remodeling and immune evasion. Furthermore, models based on ePPC-derived organoids will offer a complex platform for both basic and translational research, enabling the application of CRISPR and other advanced technologies without relying on patient samples. These models could be particularly valuable for early-stage translational studies, such as proof-of-concept experiments, as well as for investigating tumor origin, growth, and initiation processes.

Sustainable Development Goals

Masaryk University is committed to the UN Sustainable Development Goals, which aim to improve the conditions and quality of life on our planet by 2030.