Engineering cells to speed tissue repair

Replacing and repairing human tissue is becoming feasible largely due to advances in the use of stem cells. But obstacles still stand in the way of engineering these malleable cells to self-renew or expand.One of those obstacles is an incomplete picture of how cells interact with their environment.

Kelly Schultz, the P.C. Rossin Assistant Professor of Chemical and Biomolecular Engineering at Lehigh University (Bethlehem, PA - USA) recently received a three-year grant from National Institutes of Health (NIH) to study how cells remodel their microenvironment—a crucial step toward engineering cells to move through synthetic material and tissue more quickly for faster wound healing and tissue regeneration.

Schultz will build on previous work in which she and her colleagues revealed that during attachment, spreading and motility, cells degrade material in the pericellular region directly around the cell in an entirely different manner than researchers had previously believed. The results were published in an article in the Proceedings of the National Academy of Sciences (PNAS).Schultz and her colleagues made a discovery that overturned this notion. 

Before Schultz’s study, scientists believed cells moved through material while simultaneously degrading it—like Pac Man gobbling up dots while moving through a video game maze.

Schultz's team discovered that the cells pause before moving. From a stationary position, Point A, a given cell secretes an enzyme. They hypothesize that the enzyme is bound with an inhibitor that temporarily stops the enzyme from degrading the material while it’s being sent to Point B. Starting at Point B, the enzyme begins to “gobble up” the material that surrounds the cell. Only then does the cell move on to its next location.

The inhibitor, the team observed, prevents the enzyme from degrading the material while the cell is secreting it.

Schultz and her team now aim to “inhibit the inhibitor.” That is, they seek to identify which inhibitor, or combination of inhibitors, is responsible for stopping the enzyme from degrading the material while it’s being secreted. Once identified, the researchers hope to “tune” the inhibitor to shut off during secretion so that the cell will move through and degrade the material faster. This would be a fantastic breakthrough for the healthcare industry if scientists can pinpoint the inhibitor and devise a way to stop it as cells would get to the wound quicker, and regeneration could start sooner.  

“Our goal is to prevent the cell from stalling, encouraging it to become active right away and arrive at the wound site at twice the speed,” said Schultz.

(An animation by Nicolle Fuller/Sayo-Art LLC shows how cells remodel their natural environment.)

Among the nation’s brightest

Schultz is one of engineering’s rising stars, according to the prestigious National Academy of Engineering (NAE). This September, she will participate in the NAE’s 22nd annual U.S. Frontiers of Engineering (USFOE) symposium. The symposium recognizes engineers ages 30-45 who are performing exceptional research in a variety of disciplines. Schultz was one of 83 engineers from industry, academia and government to be nominated and selected for the impact of their work.

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