Wounds often heal as scar tissue rather than regenerated skin. Doctors have now found a way to influence wounds to change this process. Although it was always thought that transforming the most common type of cells found in wounds into fat cells is impossible, this is exactly what doctors have managed to do. Based on initial research done at the Perelman School of Medicine at the University of Pennsylvania, the Plikus Laboratory for Developmental and Regenerative Biology at the University of California, Irvine collaborated with Penn on a large-scale, multi-year study.

When wounds heal as scars, adipocytes (fat cells) that are normally found in the skin are lost and the most common cells found in the wounds are myofibroblasts. It was thought that these cells only form scars. Another factor that gives scar tissue an appearance different from the rest of the skin is the fact that it does not have any hair follicles associated with it. These characteristics were used by the scientists as the basis for their work. They focused on changing the myofibroblasts that is already present into fat cells that do not result in scarring.

The principal investigator of the project, George Cotsarelis, MD, is the chair of the Department of Dermatology and the Milton Bixler Hartzell Professor of Dermatology at Penn. He noted that wound healing could be manipulated so that it leads to skin regeneration rather than scarring. The key is to regenerate hair follicles first. Once that has been achieved, the signals from those follicles will stimulate the fat to regenerate.

Although hair and fat develop separately, they don’t do so independently. The Cotsarelis lab had previously discovered the factors required for the formation of hair follicles, which form first. The team has now unraveled further factors that are actually produced by the regenerating hair follicle. These factors convert the nearby myofibroblasts so that it does not form a scar, but regenerates as fat instead. That will not happen without the new hairs, but the new cells are indistinguishable from the pre-existing fat cells once it does. This gives the healed wound a natural look instead of leaving a scar. While examining what was sending the signal from the hair to the fat cells, researchers pinpointed a factor called Bone Morphogenetic Protein (BMP). BMP initiates the conversion of myofibroblasts into fat. This discovery changed what was previously known about myofibroblasts.

Comparison images of wounds healing with and without hair follicles. (Image Credit: Penn Medicine)

Cotsarelis explained that is was previously believed that myofibroblasts were incapable of becoming a different type of cell. This work does however show that these cells can be influenced and be converted into adipocytes efficiently and stably. The same result was achieved in both mouse and human keloid cells grown in culture. The study’s lead author Maksim Plikus, PhD, an assistant professor of Developmental and Cell Biology at the University of California, Irvine noted that the results show that there is a window of opportunity after an injury where the tissue can be influenced to regenerate rather than form a scar. Plikus started this research as a postdoctoral fellow in the Cotsarelis Laboratory at Penn.

These discoveries could possibly be revolutionary in the field of dermatology. The most obvious application would be to develop a therapy that signals myofibroblasts to convert into adipocytes to help wounds heal without scarring. Cotsarelis notes that this is an unmet need, although it is highly desirable from a clinical standpoint.

The increase of fat cells in tissue can however have applications other than just wounds. In treatments for HIV, adipocyte loss is a common complication and there is currently no efficient strategy for treatment. Adipocyte cells are also lost naturally due to aging, especially in the face. This leads to deep wrinkles that are permanent, something anti-aging treatments can’t fix.

Cotsarelis concludes that the results could potentially be used to formulate a new strategy to regenerate adipocytes in wrinkled skin, which could in turn result in brand new anti-aging treatments.