Researchers Unveil First Human Multi-Organ Chip to Model Metastasis

For the first time, researchers have constructed a multi-organ microphysiological system that models human metastasis with patient-derived cells and engineered bone, lung, and vascular tissues. The platform, developed at Columbia Engineering, tracks circulating breast cancer cells as they adhere to endothelium, cross into target organs, and initiate colonization—processes previously inaccessible in live patients or animal models.

Why Metastasis Has Resisted Drug Development

At least two-thirds of cancer deaths stem not from primary tumors but from metastatic spread—when cancer cells detach, enter the bloodstream, and establish secondary tumors in distant organs. Despite decades of research, therapies specifically targeting metastatic progression have shown limited clinical success. A central barrier has been the lack of predictive human models capable of revealing the dynamic, organ-specific interactions that govern this process.

Animal studies have yielded valuable insights, yet rodent biology fails to fully replicate human metastatic behavior—a discrepancy that helps explain why many treatments effective in mice falter in human trials. The new chip addresses this gap by using human-induced pluripotent stem cell (iPSC)-derived tissues, preserving species-specific molecular and cellular responses.

How the Chip Recreates Human Organ Colonization

The device features millimeter-scale compartments housing engineered human bone and lung tissues, linked by a continuously flowing vascular channel lined with human vascular endothelium. A selectively permeable endothelial barrier separates circulation from organ tissue—mimicking the physiological interface cancer cells must breach in vivo.

When introduced into the vascular channel, breast cancer cells exhibited organ-specific colonization patterns consistent with clinical observations: bone-tropic lines invaded engineered bone more aggressively and induced greater tissue degeneration, while lung-tropic lines caused pronounced damage in lung tissue but only modest colonization in bone. Molecular profiling confirmed distinct invasion signatures and secreted factor profiles across organ compartments.

What the Chip Revealed About Pre-Metastatic Conditioning

The system captured a critical early phase of metastasis known as pre-metastatic niche formation—where circulating tumor cells release signals that remodel distant organ microenvironments before physical colonization begins. Analysis of both bone and lung compartments showed measurable biochemical and structural changes induced by cancer cells prior to their arrival, confirming the chip’s ability to model this insidious preparatory step.

“Cancer is very smart, unfortunately. We learned how the cells cross barriers to get from blood circulation into the tissues,” said Gordana Vunjak-Novakovic, university professor at Columbia University and the Mikati Foundation Professor of Biomedical Engineering and Professor of Medical Sciences (in Medicine). “We were also able to reproduce something that happens in patients, where cancer cells condition the target tissues, even before they colonize them, to make them more receptive.”

A Platform for Patient-Specific Investigation

The chip accepts both patient-derived cancer cells and iPSC-engineered human tissues, enabling individualized study of metastatic behavior. Researchers can isolate variables—altering one tissue type, one signaling pathway, or one cell line—to dissect organ-specific mechanisms and identify candidate therapeutic targets.

“The pressing need for developing human tissue models of metastasis has been a key motivation for our study,” Vunjak-Novakovic said. “Our objective was to probe the ability of cancer cells to adhere to and traverse across endothelium [inner lining of blood vessels] and to determine their capacity to survive in the tissues they are colonizing through cell reprogramming and niche remodeling.”

The project involved collaboration across Columbia’s Herbert Irving Comprehensive Cancer Center, including Andrea Califano, the Clyde and Helen Wu Professor of Chemical and Systems Biology; Peter Sims, associate professor of systems biology; and Hanina Hibshoosh, professor of pathology & cell biology. Ilaria Baldassarri, a Columbia Engineering PhD student and lead author, emphasized the platform’s alignment with evolving regulatory priorities: “As the FDA and NIH place growing emphasis on new approach methodologies, this study is a concrete example of what that shift can look like in practice, applied to one of cancer’s most challenging hallmarks: metastasis.”

The study, titled “Organ-specific colonization and niche remodeling in a human tissue model of metastasis,” appeared in Science Translational Medicine on 19 August 2026. It was funded by the NIH/National Cancer Institute and the Chan Zuckerberg Initiative. DOI: 10.1126/scitranslmed.adv6871