Dr. Dana Ward recently published a new research project that is featured in the Proceedings of the National Academy of Science. The paper is entitled, “Three-dimensional biomimetic vascular model reveals a RhoA, Rac1, and N-cadherin balance in mural cell-endothelial cell-regulated barrier function.” It was a collaborative work between researchers at Harvard (Wyss Institute), Boston University, the University of Pennsylvania, the University of Washington, and Mount St. Mary’s University.
The focus is on bioengineering, in which one of the goals is trying to use engineering tools and techniques to understand how living tissues behave. She and colleagues engineered a very small blood vessel (capillary) within a chip. This chip functions similarly to a real vessel that flows fluid through it. For example, if you put in inflammatory factors, it reacts as a normal vessel would, in that vessel permeability increases meaning that the vessels leak.
Fluid from inside the vessel goes out and this is why you get swelling in areas where there is inflammation. Additional fluid accumulates in the tissue. Ward explained that through anti-inflammatory steps, the vessel would go back to normal. When you dissect the molecular pathway that could control vessel permeability, they found that the signaling that controls the cell mechanics was very important for controlling permeability.
You can study blood vessels in the body but its difficult because you cannot see them up close under the microscope. There are limitations in doing studies in the body, so that is where the chip comes in. The chip allows a better understanding of how vessels behave in inflammatory and non-inflammatory states and the factors that drive vessels to become leaky in inflammatory diseases and how this contributes to disease progression. This research can be applied to diseases such as cystic fibrosis, and cardiovascular diseases.
There is ongoing work in the Ward lab to understand the biochemical signaling pathways important for cell shape changes. Ward explains that cells must change their shape for many fundamental biological processes including cell division and cell migration. Cell division and cell migration are important for normal physiological processes like wound healing, but they are also major player in disease progression, for example, in cancer metastasis.
Another current work in progress is working with Nick Hutchings in the Visual Arts Department, with focus on 3-D printing for the chip.