Humans and other mammals are not known for their regenerative abilities, unlike organisms such as amphibians that can regrow limbs although recent research has proven that human embryonic skin can regenerate itself without leaving scar tissue. One of the main characteristics of scar tissue is an absence of hair follicles, which indicates that regeneration in a wound is a critical step to achieving scar-less skin repair. These insights have prompted efforts to define the molecular triggers that promote hair development in the skin with the ultimate goal of uncovering a method to regenerate skin both for wound healing and anti-aging therapeutic methods. The ability to induce skin regeneration rather than scarring has broad implications both clinically and cosmetically as scars are a health concern for burn victims and individuals with dermatologic conditions associated with wound healing.
Human regeneration might be linked to early development by way of a newly identified genetic factor that allows adult skin to repair like the skin of a newborn, according to emerging research. A recent study from researchers at Washington State University identifies regenerative factors in neonatal murine skin that have the potential to transform adult skin and allow it to regenerate instead of only repairing wounds with scar tissue.
Genetic Factor Lef1 Expression
The team of researchers decided to investigate the capacity of skin repair based on prior scientific literature about the early stages of mammalian life, which reveal that human embryonic skin can regenerate without leaving scars. Similarly, neonatal and adult mouse skin has been found to have the capacity to regenerate small, non-functional hair follicles under specific conditions.
Using a novel technique known as single cell RNA sequencing to compare genes and cells in developing and adult skin, the team found a transcription factor in developing skin that can influence the activation of certain genes. The factor, identified as Lef1, is associated with the ability of papillary fibroblasts to develop cells in the papillary dermis – a layer of skin that accounts for its tension and youthful appearance. When the Lef1 factor was activated, it enhanced the skin’s ability to regenerate wounds with reduced scarring and even grew new hair follicles.
When activated the factor was able to control hair follicle formation in the skin of baby mice, however, the process is mostly turned off after skin is formed and remains off in adult tissue. Although, when it was activated in adult mice, their skin was able to heal wounds without scarring, leaving reformed skin with fur and able to produce goose bumps – an ability lost in adult human scar tissue.
The implications of skin regeneration for wound healing and preventing certain aging processes could redefine the standard of dermatologic care in the future. The Washington State University investigators were able to replicate the innate ability of young, neonatal skin to regenerate, showing that this process is possible and may be replicable in human skin.
“We can still look to other organisms for inspiration, but we can also learn about regeneration by looking at ourselves,” the authors said. “We do generate new tissue, once in our life, as we are growing.”
The latest findings are a major advancement in skin regeneration medicine. Nonetheless, much research needs to be conducted further before the results can be applied to human skin. With additional funding from the National Institutes of Health, the WSU team plans to continue investigating Lef1 and other factors imperative to the skin repair process and the future of regenerative dermatology.