Fibroblasts hold clues to fat, scars and inflammation

Scientists used to think that fibroblasts – the cells that form basic tissue structures – were little more than scaffolding on which more important cells would climb. But University of Rochester Medical Center scientists have discovered that certain fibroblasts have highly specialized duties and play a major role in how scars form, fat accumulates, and harmful inflammation arises in humans.

The research is published in The American Journal of Pathology, October 2003 edition. The work may help doctors understand why some people suffer from unexplained internal scarring around vital organs, which can lead to serious diseases of the eyes, lungs, heart, kidneys or intestines. It may tell us why some accident victims and surgical patients scar easily and take longer to heal. Ultimately, the goal of the research is to pave the way toward drugs that stop unhealthy scars or fatty tissue from developing.

“This is the first clear demonstration that certain kinds of human fibroblasts can develop into scar-type or fat-type cells,” says Richard P. Phipps, Ph.D., lead author and professor, Environmental Medicine, Microbiology and Immunology, Oncology and Pediatrics. “In fact, our results show that some fibroblasts may prove to be a useful diagnostic tool by providing clues to the severity of a disease or who might be prone to abnormal wound healing, for example.”

For decades scientists generally assumed that fibroblast cells were all alike. Phipps’ group, however, began investigating subsets of fibroblasts, looking at whether they were capable of becoming specialized cells called myofibroblasts or lipofibroblasts.

Myofibroblasts are normally inconspicuous in healthy tissue but become active after injury or trauma. When uncontrolled, myofibroblasts lead to fibrosis of the liver, kidneys, lungs and heart. Lipofibroblasts have no role in scarring, but develop into fat cells and lead to thyroid eye disease and the harmful buildup of fatty tissue in the liver, spleen and bone marrow.

In the laboratory, Phipps’ group conducted experiments on fibroblasts from human uterine and eye tissue. They separated the fibroblasts, and treated the cells with an inducing agent. The scientists investigated how cells could be driven to become either the scar producers (myofibroblasts) or the fat cells (lipofibroblasts).

They discovered the surface markers that identify which fibroblasts have the potential to change and perform specialized duties. In fact, fibroblasts that express Thy-1, a protein involved in growth function, can become myofibroblasts. In contrast, cells with no Thy-1 have the potential to become lipofibroblasts.

Next, Phipps says, the group will more closely study the pathways for this cell transformation. They hope the research might lead to a medication or protein capable of blocking the buildup of fat cells or scar tissue.