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Transforming myofibroblasts to fat cells to prevent scar formation

New research shows that myofibroblasts in human skin can be induced to transform into fat cells, resulting in scar-less wound healing.

The findings, published online ahead of print in the journal Science (Jan. 5, 2017), come from research by the University of California, Irvine (UCI) and the University of Pennsylvania’s Perelman School of Medicine.

In a mouse model, investigators observed that during the wound healing process adipocytes regenerated from myofibroblasts. Myofibroblasts have been considered a differentiated cell type, and not adipogenic.

“Typically, myofibroblasts, the primary cell type found in wounds, were thought to be incapable of becoming other cell types. However, our team found that wound myofibroblasts can efficiently and stably convert into new distinct cell types, specifically new adipocytes, which are the fat-laden cells necessary for healthy skin,” Christian F. Guerrero-Juarez, a graduate student in the UCI lab who worked closely on the project, said in a press release.

The observed reprogramming of the myofibroblasts required the presence of neogenic hair follicles, that triggered bone morphogenic protein (BMP) signalling, and in turn activated adipocyte transcription factors normally expressed during development.

Guerrero-Juarez said the fact that hair follicles act as the natural source of BMPs explains why hairless wounds cannot regenerate adipocytes.

When the researchers exposed human fibroblasts—derived from keloids—in vitro to either BMP or to human hair follicles, it triggered reprogramming of the cells toward new adipocytes, demonstrating that the findings in the mouse model are translatable to humans.

“Essentially, we can manipulate wound healing so that it leads to skin regeneration rather than scarring,” Dr. George Cotsarelis, chair of dermatology and Milton Bixler Hartzell Professor of Dermatology at the University of Pennsylvania and principal investigator on the project, said. “The secret is to regenerate hair follicles first. After that, the fat will regenerate in response to the signals from those follicles.”

Maksim Plikus, an assistant professor of developmental & cell biology at UCI and lead author on the paper, noted that regenerating fat cells in skin may be beneficial for conditions other than scarring, such as reducing wrinkles resulting from loss of skin fat with age.

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