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Center for Cell Dynamics
on having the right tools to watch an epithelial tissue remodel its architecture:
Would it be accurate to say that technological advances have largely driven this field?
EWALD: Yes. It's been a combination of organotypic culture, a method for growing cells in three dimensions; more powerful microscopy; and molecular imaging, making the types of molecules that allow you to label and see cells building tissues in real time. The strength of the Center for Cell Dynamics is being able to bring together people in all of these different disciplines.
What does organotypic culture allow you to do that conventional cell culture does not?
EWALD: No cell is an island unto itself. Scientists have learned a great deal about cell migration by growing cells on Petri dishes. But that technique sacrifices the tissue and organ context.
In organotypic culture, also called biomimetic culture, we take pieces of tissue and grow them in a gel on a dish. The gel acts like a scaffolding that allows multiple cell types to grow in three dimensions, as they would in vivo.
How do you customize the microscopes you use in your studies?
EWALD: Mainly, that involves minimizing the moving parts. The confocal microscope needs to be mechanically stable for hours at a time. We might take 20 to 100 movies over the course of 20 to 100 hours. We do continuous bright-field imaging of some cultures for 10 to 15 days, and we might view a culture from 20 to 100 different positions.
It takes a mouse five to seven weeks to build a mammary gland. We want to see a good portion of that process in our cultures.
How might your research be applied medically?
EWALD: The hope is to use these cultures to understand what's molecularly required for tumors to grow and invade distant sites. By understanding how tumors grow, at the cellular and molecular level, we hope to identify molecules we can interfere with, and ideally halt metastasis.
We are also pursuing a theory that cancer in the mammary gland may simply occur when a normal morphogenetic process occurs at the wrong time and in the wrong place. For instance, epithelial cells may begin building multilayered structures when what's called for is a bilayered structure. If this growth continues, it could lead to cancer.
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