Skin Regeneration in Wound Repair

by Madeline Bradley

Unlike some lower invertebrates, like fish and amphibians, which can regenerate all the skin layers and appendages (epidermis, dermis, hair follicles, sebaceous glands, etc.) perfectly, human skin often forms thin scar tissue lacking in appendages.1 The deformed appearance alone can take a serious toll on the quality of life for burn patients and amputees, but scar formation also compromises the skin’s further functions as a sensory and thermoregulatory organ.2 Researchers, recognizing the enormous value in improving wound recovery, are actively investigating the area of normal growth versus wound recovery.

One lab devoted to this research exists here on Harvard’s campus. The Hsu Lab, led by principal investigator Ya-Chieh Hsu, aims to examine fundamental questions, such as how skin cells know when to start and stop proliferation after wound damage, as well as more complicated questions like why hair follicles cannot regenerate themselves after skin damage. By examining factors in normal and wound regeneration, they hope to learn more about the similarities and differences between the two types, which would lead to a better understanding of why skin does not grow back properly after injury. Ultimately, a better understanding could lead to advances in regenerating more functional skin.

The Hsu Lab primarily uses mouse models to study regeneration. Using ultrasound-guided probes, the researchers can directly inject genes of interest that act as skin-damaging factors into the developing embryos of a pregnant mouse. The mouse resultantly gives birth to mice with compromised skin, which the researchers can then study as it repairs itself. The researchers also sometimes graft human skin onto the mice to study it more directly.

The researchers have gleaned multiple insights from the experiments thus far, one of them highlighting the critical role hair follicles play in skin growth. Hsu and her team found that when hair follicles grow in normal skin, they grow downward, pushing deeper into the skin, a development that in itself acts as the driving force of skin thickening.1 Thus, when hair follicles get damaged and cannot regenerate, the skin no longer has that force pushing it to thicken. Hsu’s team believes this finding shows that hair follicle regeneration failure is why scar tissue grows thinner than normal skin.

Furthermore, hair follicles function as an integral signal in a complex communication network between the plethora of different cell types within skin, and examining how they communicate with each other is another thriving aspect of current research.3 Hsu explained that in normal skin, hair follicles act as a sort of anchor for the nerve cells, allowing them to target the hair follicles to receive information such as sensory signals. In scar tissue, however, nerve endings have no hair follicles to target, leading to an impaired sense of touch in that injured region. The critical role of hair follicles in normal skin function necessitates that skin research is intertwined with that of hair follicle regeneration.3

Keeping this research duality in mind, Hsu and her colleagues also found that overexpression of SHH, a gene that makes a protein called Sonic hedgehog, stimulates hair follicle stem cell proliferation.3 Sonic hedgehog functions as a chemical signal essential to developing the dorsal-ventral axis pattern during embryonic development, and it has other functions in cell growth and cell specialization.4 This discovery of its additional role in hair follicle stem cell proliferation marks an exciting development in the potential to improve treatment, as future research could hone in on whether SHH could be used to recover hair follicle growth in damaged skin.

The ability to improve skin functionality and appearance gives the potential for great increases in the quality of life for burn victims and other patients suffering major skin damage. Researchers will likely keep uncovering factors and pathways in normal regeneration that are missing or damaged in wound regeneration, allowing them to target areas that need improvement and come closer than ever to completely functional skin recovery.

Madeline Bradley ’18 is a sophomore in Eliot House.

Works Cited

  1. Takeo, M. et al. Perspectives in Medicine. 2015, 5(1).
  2. Hsu, Y.-C. et al. Nature Medicine. 2014, 20(8), 847–856.
  3. Hsu, Ya-Chieh. (2015 September 30). Skin Regeneration Research. Personal interview.
  4. SHH gene. Genetics Home Reference. U.S. National Library of Medicine.




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