Human multi-organ chip models breast cancer spread to bone and lung

Researchers at Columbia University have developed a multi-organ chip that models how breast cancer cells spread through the bloodstream to colonize bone and lung tissue. The device, described in Science Translational Medicine, connects millimeter-scale engineered human bone, lung, and vascular endothelium in a single microfluidic platform with circulating flow.

The chip was built using induced pluripotent stem cells differentiated into tissue-specific compartments, each maintained in optimized bioreactor conditions. A selectively permeable endothelial barrier separates the vascular channel from the tissue compartments, mimicking the interface cancer cells must cross during metastasis.

When researchers introduced human breast cancer cells into the vascular circulation, the cells displayed organ-specific colonization patterns consistent with clinical observations. Bone-tropic cells colonized bone more aggressively and induced pronounced bone degeneration, while lung-tropic cells disrupted lung tissue more severely and showed only modest bone colonization.

The platform also captured pre-metastatic niche formation, where cancer cells condition distant organs to become more receptive to colonization before the cells physically arrive. Signs of this remodeling were detected in both bone and lung compartments.

The study was led by Gordana Vunjak-Novakovic's Laboratory for Stem Cells and Tissue Engineering in collaboration with Columbia's Herbert Irving Comprehensive Cancer Center. Doctoral student Ilaria Baldassarri noted the model aligns with growing FDA and NIH emphasis on new approach methodologies that can complement or reduce reliance on animal models.

Metastasis accounts for at least two-thirds of cancer deaths, and drugs targeting metastatic progression have largely failed in clinical trials. The researchers argue that species differences between humans and rodents limit the predictive value of animal models for studying human metastatic mechanisms.

The chip enables controlled experimentation with actual patient cells and tissues within organ-specific microenvironments. This allows investigation of molecular pathways and therapeutic targets for metastasis that are difficult to access in animal models or static cell cultures.

The work demonstrates a human, patient-specific platform for studying organ colonization, a critical and poorly understood phase of metastasis. The researchers plan to use the system to probe how cancer cells traverse endothelium, survive in new tissues, and reprogram the metastatic niche.