Investigation of Cell-cell Interactions via Compartmentalized Co-culture Platforms

Posted by

SELECTBIO

Intercellular communication is strongly dependent on the spatial organization of tissues at the micrometer scale. We present microfabricated cell culture substrates that enable fine-grained control of cell positioning, allowing the investigation of contact-dependent signaling dynamics, short-range paracrine effects, and feedback signaling. Reconfigurable comb substrates allow two cell populations to be co-cultured either in direct contact or close proximity without contact; pure populations can also be quickly recovered from the co-culture. The system was originally developed for the study of cell-cell interactions in the liver, where we discovered the importance of direct contact as well as the temporal length of contact. More recently, we have discovered short-range paracrine effects in tumor-stromal culture and ES-feeder culture. In the cancer system, this provides a platform for high-throughput profiling of effects from tumor-stromal crosstalk. In the stem cell system, this provides an unmixed feeder-layer system for maintaining pluripotency without contamination of the ES cells by the feeders.