UK Team Receives NIH Award to Explore How Macrophage Phenotypes Influence Tissue Regeneration

LEXINGTON, Ky. (May 17, 2017) — Tissue regeneration is complex and involves the dynamic interaction of many cellular and physiological processes. Understanding how these processes interact to regulate regeneration requires working across disciplines. In support of an interdisciplinary approach, the National Institutes of Health (NIH) recently awarded researchers at the University of Kentucky a five-year, $1.65 million grant from its National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) to study how inflammatory cells can regulate tissue regeneration in mammals.

The research team is led by Ashley Seifert, assistant professor of biology in the UK College of Arts and Sciences, and John Gensel, assistant professor of physiology in the UK College of Medicine. The goal of the research is to understand how different immune cell types promote regenerative outcomes in response to injury.  Ultimately, this basic research may aid clinicians in designing novel approaches to restore damaged tissue in humans.

Despite clinical advances, the fact remains that humans cannot regenerate injured tissue. Instead, tissue trauma stimulates inflammation, which in turn induces fibrosis and ultimately the formation of scar tissue. The project, “Macrophage Phenotype Orchestrates Mammalian Tissue Regeneration,” will leverage an emerging model of mammalian tissue regeneration, the African spiny mice. The new award will help the researchers determine how macrophages, a type of inflammatory cell found at the site of injury, regulate fibrosis or regeneration.

The group will compare the African spiny mice, which have the natural ability to regenerate skin, hair follicles, nerves, muscle and cartilage in their external ears, with laboratory mice which heal identical ear or skin injuries with scar tissue.  By studying both rodent species, the researchers will determine which macrophage subtypes regulate regeneration and scarring, and how.

“If we want to apply what we learn from basic regenerative biology to humans it would be helpful to understand what cell types and molecules regulate regeneration in a mammal where it occurs naturally,” Seifert said.

By identifying subtypes that regulate regeneration, the group aims to manipulate the macrophage phenotypes in laboratory mice towards a pro-regenerative outcome.

“There is growing appreciation that macrophages can adopt both regenerative and pathological functions,” Gensel said. “Since we are actively developing clinically feasible therapies that selectively activate macrophages, identifying targetable components of macrophage activation opens new areas of discovery with real potential for improving tissue regeneration in humans.”

The research is expected to provide new and fundamental insight into how macrophages coordinate the inflammatory and immune reaction to stimulate a regenerative response to injury.

The team's previous study on regeneration and macrophages was also published this week in eLife. Read more at