Minimal Scarring…possible: some Fibroblasts are Guilty

Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.
Rinkevich Y, Walmsley GG, Hu MS, Maan ZN, Newman AM, Drukker M, Januszyk M, Krampitz GW, Gurtner GC, Lorenz HP, Weissman IL, Longaker MT.
Science. 2015 Apr 17;348(6232):aaa2151. doi: 10.1126/science.aaa2151.

“Will I get a scar from the procedure ?” – a question that often comes up

Fibroblasts…

• …are the cells building up the dermis. They are embryologically derived from the mesoderm*.
• …secrete structural components of the dermis (extracellular matrix), which consists of collagen, hyaluronic acid….components which are responsible for the tensile strength and aspect of the skin. A reduction of their activity results for example in loss of volume such as that which is seen in aging.
• …play an indispensable role, yet are poorly understood. However, this study done in mice shows that there are at least 2 lineages of fibroblasts (in mice), and that one of them  (so called fibrogenic fibroblasts) is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation.

• In this US study published in Science, the Key findings are as follows:
  • The Engrailed-1 (En1) gene is expressed in fibrogenic lines of fibroblasts.
  • By using transgenic mice expressing the diphteria toxin receptor and adding diphtheria toxin the En1 lineage is removed and henceforward leads to diminished connective tissue deposition in wounds and significantly reduces melanoma growth in the dorsal skin of mice.
    • Although scarring formation is decreased, the tensile strength of the wound is maintained, suggesting that the wound remains functional.
  • Identified surface marker of this lineage of fibroblasts: CD26/dipeptidyl peptidase-4 (DPP4).
  • Small molecule–based inhibition of CD26/DPP4 enzymatic activity in the wound bed of wild-type mice during wound healing results in diminished cutaneous scarring after surgical excisional-induced wounding.
  • Conclusion
    • Although done in mice, understanding of the presence of specific populations of fibroblasts responsible for scar formation (fibrogenesis) brings a new perspective in the treatment of wounds healing (scar prevention).
    • The results of this research in mice can perhaps be extrapolated to understanding and treating fibrotic disease, cancer progression in humans.

*Other cells derived from the mesoderm: Langerhans’ cells, macrophages, mast cells, fibroblasts, blood vessels, lymph vessels, muscles, and adipocytes.

Article selection: Prof Dr Jean-Hilaire Saurat – dermatologist. Geneva, Switzerland