Reprogramming Fibroblasts Promotes Scarless Healing

A groundbreaking study shows that myofibroblasts can be transformed into adipocytes during wound healing, resulting in regenerated skin rather than scar tissue.

Researchers at the University of Pennsylvania, the University of California Irvine, and other institutions discovered in a mouse model that myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling. This, in turn, activated adipocyte transcription factors that are expressed during development, instructing the myofibroblasts to become fat cells. Overexpression of the BMP antagonist, noggin, or deletion of the BMP receptor in the myofibroblasts prevented adipocyte formation.

The researchers showed that the process was dependent on the presence of hair follicles. Adipose cells will not form without new hairs, but once they do, the new cells are indistinguishable from pre–existing fat cells, giving the healed wound a natural look instead of leaving a scar. The researchers added that the increase of fat cells in tissue can also be helpful for conditions that induce adipocyte loss, such as HIV treatment, or for filling in permanent, deep wrinkles. The study was published on January 5, 2017, in Science.

“The secret is to regenerate hair follicles first. After that, the fat will regenerate in response to the signals from those follicles,” said senior author professor of dermatology George Cotsarelis, MD, of Penn. “Our work shows we have the ability to influence myofibroblasts, and that they can be efficiently and stably converted into adipocytes. This was shown in both the mouse and in human keloid cells grown in culture.”

Scars are areas of fibrous tissue that replace normal skin after injury. Apart from very minor lesions, every wound results in some degree of scarring. The scar tissue is composed of collagen, but the fiber composition is different; instead of the normal, random, basket-weave formation of the collagen fibers found in normal tissue, the collagen cross-links and forms a pronounced alignment in a single direction, which results in inferior functional quality.