Engineering patient-centric Organoid and Organ-on-a-Chip Models for Cancer Research

Over the past decade, patient-derived organoids have emerged as versatile tools for disease modeling especially in cancer research, offering the ability to expand healthy and diseased human tissue from various organs.

As this research field matures towards addition of more components of the tumor microenvironment for accurate disease modeling, bioengineering solutions like organs-on-a-chip take center stage for building more complex patient-derived models. In such organs-on-a-chip, different populations of human cells can be seeded into microfluidic devices, allowing for the assessment of their interactions under programmable and tightly controlled conditions designed to recapitulate the physiological setting as closely as possible. Organoids have proven to be an excellent means to expand and characterize patient-derived cells, thereby serving as a “bioink” to populate organ-on-a-chip and other bioengineering systems.

As our flagship project in organ-on-a-chip bioengineering, we have established an integrated microbiome-colorectal tumor-microvasculature chip to study bacterial roles in the earliest stages of colorectal cancer (CRC) metastasis formation (see Figure). In this use case, we incorporate constitutive genetic fluorescent labels into healthy and cancerous colon organoids from the same patient and seed them on the Emulate organ-on-a-chip platform. On the chip, epithelial cells are connected to human intestinal microvasculature from the basolateral side, while candidate CRC-derived bacteria are flushed along their apical side. This chip serves as the first in vitro platform to assess bacterial interaction with healthy and cancerous colon epithelium and the consequent changes in local vasculature interaction.