Decellularized Tissue Scaffold: a Novel Platform for Expanding Circulating Tumor Cells of Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival rate of around 10%, largely due to late diagnosis and the inability to monitor treatment response with sufficient precision. Circulating tumor cells (CTCs) from patient blood samples offer a minimally invasive method for tracking tumor evolution; however, their rarity and contamination by blood cells limit the accuracy of molecular profiling and functional studies. The expansion of patient-derived CTCs could overcome these barriers, yet current methods have shown limited success.

We developed a novel platform using decellularized lung extracellular matrix (dECM) to provide a physiologically relevant microenvironment for PDAC CTC proliferation. Lung tissue, a frequent metastatic site in PDAC, was obtained with informed consent during patient surgery, sectioned, and decellularized, preserving the original structure and key adhesion proteins. Using as few as ~500 spiked Panc-1 cells, the system is tested to support robust cell proliferation, maintain epithelial characteristics, and preserve KRAS mutation allele frequencies, demonstrating genomic stability.

A major milestone of this study is the success in real patient samples: isolated plasma-derived CTCs from PDAC patients were successfully expanded ex vivo on dECM using minimal starting material, obtained from 1 mL of blood and 50-micron-thick tissue slices. To our knowledge, this represents one of the first successful demonstrations of CTC expansion via decellularization technology, and with exceptionally low input cell numbers.

This breakthrough opens the door to longitudinal, patient-specific tumor modeling, enabling drug sensitivity testing, metastasis research, and real-time monitoring of therapeutic response. By bridging tissue engineering and liquid biopsy, our platform addresses a critical unmet need in PDAC research and has broad potential for application in other cancers where CTCs can be isolated.