Defensins and the dermis

November 13, 2019

Research shows activating LGR6+ stem cells with defensins repopulates the epidermis with fresh keratinocytes for visible improvement.

Wound healing is complex. Injured tissues undergo a multi-phase process from hemostasis to tissue remodeling. And defensin plays a role. 

“Basically, it's your natural mechanism for healing a wound, and it stimulates a specific stem cell, the LGR6+ stem cell,” according to Greg Keller, M.D., who presented “Clinical Data with Defensins” at the Global Aesthetic Conference in Miami earlier this month.

“After activation, LGR6+ stem cells physically migrate into the basal layer of the skin and create a new epidermis, and eventually, new, younger-acting skin,” says Dr. Keller.

In her Cosmeceutical Critique of “The role of defensins in treating skin aging,” Leslie Baumann, M.D., writes, “LGR6+ stem cells, which are dormant until they are activated to respond to damage, are stimulated by defensins.”1

She effectively summarizes their role in anti-aging as:

• Old fibroblast and keratinocytes are sluggish and lazy.
• Old cells do not “hear” signals as well as younger cells.
• LGR6+ stem cells repopulate the epidermis with new, young keratinocytes.
• Defensin stimulates LGR6+ stem cells.
• The defensin/LGR6+ pathway plays a role in keratinization.
• Using topical defensin can improve the skin’s appearance.

Theoretically, says Dr. Keller, hair follicles provide a way for defensins to enter the skin to activate the LGR6+ pathway, but “We wanted to … actually measure wrinkles and quantify… how much better the skin was in terms of pore size, oiliness, wrinkles, and the like.”

So he, Amy Taub, M.D., Vivian Bucay, M.D., Jay Williams, Ph.D, and Darius Mehregan, M.D., conducted a participant- and investigator-blinded, placebo-controlled, multi-center study with the defensin-containing DefenAge 3-step system (Progenitor Biologics) that includes the 2-Minute Reveal Masque, 24/7 Barrier Balance Cream and 8-in-1 BioSerum, on 44 women, 41-71 years of age with skin types I to V.2

 

They performed evaluations at baseline, 6 and 12 weeks, using a combination of histopathology and immunochemistry, Griffiths scale and high-resolution photography to evaluate skin. A 15-patient subset also received 3-dimentiosional imaging with the QuantifiCare system and Cortex measurements.

Quantificare, says Dr. Keller, has both an existing data base to provide a skin reference and a three-dimensional device that measures wrinkles, and allowed them to look at the effect of defensins on the skin objectively.

“We found thickening of the dermis of the skin, reestablishment of rete pegs and generally a younger skin, which we’d seen in our initial claims,” explains Dr. Keller.

“This actually became an age difference within QuantifiCare's database of 16 years. We actually made the skin 16 years younger,” he says. “And so, one of the things that we came away with was, not only did we like what Defenage did… but we also liked the ability and felt good about making claims that we could document through the QuantifiCare analysis.”

Overall, the researchers found statistically significant improvement in the treatment vs placebo group for visible pores, hyperpigmentation, both superficial and deep wrinkles and epidermal thickness.

“The effect on pores was amazing… we think largely because of the thickening of the skin pushing the pores together.” says Dr. Keller.

Notably, while retinols and other skin rejuvenating treatments may cause inflammation, says Dr. Keller, “…this doesn’t because it stimulates the LGR6 stem cell directly to produce new skin.”

References:

1. Taub A, Bucay V, Keller G, Williams J, Mehregan D. Multi-Center, Double-Blind, Vehicle-Controlled Clinical Trial of an Alpha and Beta Defensin-Containing Anti-Aging Skin Care Regimen With Clinical, Histopathologic, Immunohistochemical, Photographic, and Ultrasound Evaluation. J Drugs Dermatol. 2018;17(4):426-441.
2. Bauman L. The role of defensins in treating skin aging. Cosmeceutical Critique. MDedge Dermatology. April 1, 2018. Accessed November 13, 2019. Available at: https://www.mdedge.com/dermatology/article/161149/aesthetic-dermatology/role-defensins-treating-skin-aging/page/0/1