If we could engineer human organs and other tissues, we could move beyond the need for donor organs and perhaps screen potential new medical therapies on manufactured tissues before going into clinical trials. Unfortunately, however, the complexity of how different types of human tissue knit themselves together poses a key challenge to programmed assembly.
Alex Hughes, a postdoctoral researcher in the Gartner Lab at the University of California, San Francisco, wants to figure out the “design rules” that govern this cellular self-assembly. His paper — “Tissue origami: Directed folding of tissues by programmed cell contractility networks” – was a highlight at Monday’s minisymposium “Connecting Cells to Tissues.”
While it might initially make sense to try to construct complex tissue from its various component cells, biology doesn’t really work that way. Instead, Hughes and his colleagues have begun to decipher how and why different types of tissue cells can be induced to interact, causing buckling and natural shape-shifting to occur.
“It can be difficult to tell which events are important by reviewing them in isolation,” Hughes told the audience. So his group mimics natural biological processes, growing different cell types together in extracellular matrices to see how they interact.
Fibroblasts, they’ve learned, serve as actuators to pull fibers into alignment, compact and align collagen, and cause mechanical interactions that buckle tissue, causing it to curve along a specified axis.
So far, the group has developed engineering control over three-dimensional tissue shapes using extracellular matrix scaffolds. They hope to use this “tissue origami” to improve drug toxicity screens and study compound tissue development in greater detail.