To build organ chips, in the past Wyss teams have combined multiple types of cells from an organ on a plastic microfluidic device, while steadily supplying nutrients, removing waste, and applying mechanical forces the tissues would face in the body. But bone marrow is so complex that they needed a new approach to mimic organ function.
This complexity arises because bone marrow has an integral relationship with bone. Marrow sits inside trabecular bone a solid-looking type of bone with a porous, honeycombed interior. Throughout the honeycomb, conditions vary. Some areas are warmer, some cooler; some are oxygen-rich, others oxygen-starved, and the dozen or so cell types each have their own preferred spots. To add complexity, bone marrow cells communicate with each other by secreting and sensing a variety of biomolecules, which act locally to tell them whether to live, die, specialize or multiply.
Rather than trying to reproduce such a complex structure cell by cell, the researchers enlisted mice to do it.
"We figured, why not allow Mother Nature to help us build what she already knows how to build," said Catherine S. Spina, an M.D.-Ph.D. candidate at Boston University, researcher at the Wyss Institute, and co-lead author of the paper.
Specifically, Wyss Institute Postdoctoral Fellow Yu-suke Torisawa and Spina packed dried bone powder into an open, ring-shaped mold the size of a coin battery, and implanted the mold under the skin on the animal's back.
After eight weeks, they surgically removed the disk-shaped bone that had formed in the mold and examined it with a specialized CAT scanner. The scan showed a honeycomb-like structure that looked identical to natural trabecular bone.
The marrow looked like the real
|Contact: Dan Ferber|
Wyss Institute for Biologically Inspired Engineering at Harvard