‘Bad guy’ fibrocytes could help rebuild damaged tissue

May 10, 2019

A new study by a University of Wisconsin School of Medicine and Public Health researcher shows that someday, fibrocytes may be used for regenerative therapies for people who need to have their vocal folds or other tissues rebuilt after damage or loss.

Nathan Welham, associate professor of surgery, and colleagues published their study of fibrocytes this week in the journal Science Advances.

In 2015, Welham created an artificial vocal fold that drew worldwide media attention. His laboratory used larynx cells from cadavers and surgical patients to grow transplantable tissue that created voice-like sound when vibrated. His current study arose from a search for other types of cells that could be easily harvested from a patient’s own body and grown to make new tissues.

Until recently, the process by which fibrocytes differentiate from monocytes was “a black box and poorly understood,’’ Welham says. “We wondered if we could shed some light on the differentiation process and, additionally, use the resulting mesenchymal cells for a therapeutic purpose. Could these cells have a good side?”

One part of the study described how the fibrocytes go through a 14-day process of transforming from a round monocyte cell to an elongated mesenchymal cell. Next, they used proteomics to identify the proteins associated with this transformation. They showed that differentiation involves a complete retooling of cell metabolism, including greater dependence on a pathway called oxidative phosphorylation. They then compared the cells to other mesenchymal cell types, including cells obtained from skin, vocal fold, and bone marrow, finding that at the proteome level, they are distinct, although fibrocytes do have some mesenchymal features.

Next, they tried using the mature fibrocytes to build multilayered tissues. They placed the cells within a scaffold to form a base layer, put epithelial cells on top, and found that the layer built from fibrocytes was able to support the maturation of a functional epithelium. They were less successful when they tried to also make the epithelium using blood-derived fibrocytes.

Another part of the study looked at the role fibrocytes play in wound healing. In one test, the researchers simulated an injury and studied how local cells move in and repopulate an artificial wound. Through a series of experiments, they showed that fibrocytes send a protein called CXCL8 as a signal to spur the migration of local cells during wound healing.

University of Wisconsin-Madison has the full article