What doctors once thought was impossible to do in humans was recently found possible in a large-scale, multi-year study. There is now a way to manipulate wounds to heal as regenerated skin as opposed to scar tissue by transforming the most common type of cells found in wounds into fat cells.
Researchers started this study at the Perelman School of Medicine at the University of Pennsylvania in connection with the Plikus Laboratory for Developmental and Regenerative Biology at the University of California, Irvine.
Bring on the Myofibroblasts
Adipocytes—another term for fat cells—are found in the skin. However, when wounds heal as scars, adipocytes are then lost. Thought to only form from scars, myofibroblasts are the cells most commonly found in healing wounds. Skin also has an unusual appearance when scarred, as hair follicles are not associated to these types of wounds.
Researchers were able to take this information and change myofibroblasts into fat cells without scarring.
George Cotsarelis, M.D., the chair of the Department of Dermatology and the Milton Bixler Hartzell Professor of Dermatology at Penn and the principal investigator of the project explained this newfound method.
"Essentially, we can manipulate wound healing so that it leads to skin regeneration rather than scarring," said Cotsarelis. "The secret is to regenerate hair follicles first. After that, the fat will regenerate in response to the signals from those follicles."
Developing Hair and Fat
Cotsarelis and researchers discovered hair follicles form separately from fat, but not independently. Being the first to form, hair follicles have certain factors to convert surrounding myofibroblasts to regenerate as fat as opposed to forming a tissue scar. The healed wound will be left with a natural appearance rather than a scar once the new cells are indistinguishable from pre-existing fat cells.
The team of researchers also found the bone morphogenetic protein (BMP), which sends instruction for the myofibroblasts to become fat.
"Typically, myofibroblasts were thought to be incapable of becoming a different type of cell," explained Cotsarelis. "But our work shows we have the ability to influence these cells, 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.
Starting this research as a postdoctoral fellow in the Cotsarelis Laboratory at Penn, the study's lead author, Maksim Plikus, Ph.D. is an assistant professor of Developmental and Cell Biology at the University of California, Irvine. The two institutions continued their collaboration and Plikus added his insight for the study as well.
"The findings show we have a window of opportunity after wounding to influence the tissue to regenerate rather than scar," said Plikus.
Progression in Dermatology and Additional Treatment
This study could benefit dermatologists, estheticians, spa owners and professionals and so forth with a therapy that signals myofibroblasts to alter into adipocytes to help wounds heal without any scars.
"It's highly desirable from a clinical standpoint, but right now it's an unmet need," said Cotsarelis.
The increase of fat cells can benefit not only wounds, but also other conditions, such as HIV. However, researchers have not yet found the right approach for this type of treatment.
Adipocyte can also be lost naturally due to aging, which leads to wrinkles cosmetics cannot repair.
"Our findings can potentially move us toward a new strategy to regenerate adipocytes in wrinkled skin, which could lead us to brand new anti-aging treatments," Cotsarelis said.
Lab Work and Further Research
While the Cotsarelis Lab is looking into what tools can promote skin regeneration, specifically with respect to hair follicle regeneration, the Plikus Laboratory is studying other facets of cell reprogramming in skin wounds.
The Plikus Laboratory researchers are investigating the role of other signaling factory beyond BMP in addition to researching further studies using human cells and human scar tissue.