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Study Reveals How Protein Norrin Helps Activate Hair Growth


DURHAM, N.C. (
JUNE 25, 2019)A study released today in STEM CELLS identifies a possible new way to regrow hair. The research demonstrates how extracellular vesicles (EVs), isolated from stimulated dermal fibroblasts, promote hair growth via their secretion of the protein norrin — and how norrin is a key player in growing hair.

The discovery could lead to numerous therapeutic treatments for alopecia (hair loss), the researchers say.

Alopecia is a problem impacting millions of people that not only affects their psychological well-being, but endangers certain skin functions, too. Currently available treatments, however — including drugs and transplants — have numerous limitations, leaving scientists searching for other solutions.

Dermal papilla cells, found at the root of a hair follicle, are of interest in this regard as they control the growth and regeneration of the follicles. In part, this is achieved through cell-to-cell communication. Some scientists believe this communication occurs via extracellular vesicles (EVs) secreted by the surrounding cutaneous (skin) cells.

While numerous functions have been attributed to EVs in physiology and pathology, few studies have examined their impact on hair follicles. What scientists do know about EVs and hair is that EVs from dermal papilla cells are able to stimulate the proliferation and migration of follicular keratinocytes (the cells responsible for forming tight junctions with the nerves of the skin). One recent study on mice also showed that EVs from bone marrow-derived mesenchymal stem cells or dermal papilla activated hair growth in the animals, but neither the underlying molecular mechanism nor the mediator molecule(s) behind this were identified.

In the study published in STEM CELLS, a research team led by Daniel Aberdam, Ph.D., of INSERM and the Université de Paris, decided to tackle these questions. In particular, they wanted to investigate the role of EVs isolated from stimulated human dermal fibroblasts in activating dermal papilla cells to promote hair growth.

The results of their study show how activated dermal fibroblasts secrete specific EVs (st-EVs) that enhance hair follicle growth ex vivo. They demonstrate that st-EVs stimulate dermal papilla cells to secrete Norrin, which in turn activates follicular keratinocytes. Norrin is known to play a role in Wnt/-catenin signaling, which previous studies have shown to regulate hair growth.

"Remarkably, norrin-specific receptor, called Frizzled4, is absent from follicular keratinocytes. We showed here that dermal fibroblast EVs carry at their surface Frizzled4 to allow Norrin signaling and hair growth,” Dr. Aberdam said. “As such, our study identifies dermal fibroblast EVs as efficient activators of dermal papilla cells, and norrin as a novel player in regulating hair growth in normal and pathological conditions”.

Dr. Jan Nolta, Editor-in-Chief of STEM CELLS, said, “The detailed molecular studies reported by the Aberdam group have uncovered a deeper level of signaling by extracellular vesicles to promote hair growth. The involvement of frizzled4 and norrin in this pathway is highly important for the development of novel therapies.”

Full Image caption: Microvesicles (EVs) are secreted by dermal fibroblasts (DF) (1) to activate norrin secretion by dermal papilla (DP) cells (2). In turn, Norrin activates follicular keratinocytes (fKer) through its Fzd4 receptor provided by dermal fibroblasts EVs (3) to enhance beta-catenin pathway and hair follicle growth (4).

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The full article, “Extracellular vesicles from activated dermal fibroblasts stimulate hair follicle growth through dermal papilla-secreted norrin,” can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/stem.3043.

About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS® (http://www.StemCells.com) is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST® (http://www.TheOncologist.com) is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE® (http://www.StemCellsTM.com) is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

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