Bernstein Medical - Center for Hair Restoration - Dermal Papilla

Dermal Papilla

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Could a hormone that plays a critical role in red blood cell production also play a critical role in hair follicle production? According to a 2010 research report published in the Journal of Dermatological Science, this may be the case.

Erythropoietin Implicated In Hair Growth Regulation

The hormone in question is called Erythropoietin (EPO). It is produced in the kidneys in order to regulate red blood cell production. Recent studies have shown that EPO is also produced in a structure that surrounds and protects a hair follicle, the outer root sheath (ORS). Moreover, other studies have found that the EOP secreted by the ORS seems to target dermal papilla (DP) cells. DP cells play a critical role in regulating hair growth.

Because of these results, researchers have speculated that EPO may affect hair growth by acting on DP cells, but no direct evidence for this had ever been found – until now.

Evidence That EPO Affects Hair Growth in Vitro (Cell Cultures)

Strong evidence of EPO’s direct involvement in hair growth would be the discovery of EPO receptor sites (EPOR) on DP cells and a clear mechanism of how EPO affects changes in a DP cell (called cell signaling); this is exactly what researchers in the Republic of Korea ((Kang BM, Shin SH, Kwack MH, Shin H, Oh JW, Kim J, Moon C, Moon C, Kim JC, Kim MK, Sung YK. Erythropoietin promotes hair shaft growth in cultured human hair follicles and modulates hair growth in mice. J Dermatol Sci. 2010 Aug;59(2):86-90. doi: 10.1016/j.jdermsci.2010.04.015. Epub 2010 May 19.)) have found. Not only did they find direct evidence of EPO receptive sites but they also discovered the critical cell signaling mechanism: phosphorylated EPOR signaling pathway mediators.

In addition to discovering the signaling mechanism, they also showed using cell cultures that EPO causes both dermal papilla to proliferate and hair shafts of human hair follicles to elongate.

While the effects of EPO on DP and hair follicles were compelling, they only occurred in vitro (in cell cultures outside the body) and it is known that cells cultured on a flat surface behave significantly differently than cells that exist in situ, inside the organism (see Higgins and Christiano, Regenerative Medicine And Hair Loss: How Hair Follicle Culture Has Advanced Our Understanding Of Treatment Options For Androgenetic Alopecia).

Evidence That EPO Affects Hair Growth In Situ (In The Body)

In order to better answer the questions of whether and how EPO might directly affect hair growth in situ, the Korean researchers implanted EPO treated DP cells into mice and found that these treated cells not only moved hair follicles from their resting (telogen) phase into an active hair growth (anagen) phase but also prolonged a follicle’s active growth phase.

This is a significant finding since one of the mechanisms of male pattern baldness is DHT susceptible hair follicles entering into progressively longer periods of a telogen (resting) phase relative to an anagen (hair growth) phase. EPO, having the opposite effect on hair follicles, opens the door to treating this type of hair loss with existing EPO analogs and/or developing new erythropoietin biopharmaceuticals.

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We have previously discussed Dr. Angela Christiano‘s work on hair loss genetics with her team at Columbia University in New York. A review of the 16th annual meeting of the European Hair Research Society; held recently in Barcelona, Spain; brings to our attention new research being conducted by a very astute scientist, Dr. Claire Higgins, who works at Dr. Christiano’s laboratory.

With tissue supplied by Bernstein Medical, Dr. Higgins is studying the inductive properties of the dermal papilla (DP), a group of cells that forms the structure directly below each hair follicle. As outlined in our Hair Cloning Methods page, the dermal papilla is of great interest to hair restoration physicians. Ideally, research of this kind will lead to a breakthrough in hair cloning or hair multiplication which will allow physicians to effectively “cure” hair loss by developing a limitless supply of donor hair that can be used in hair restoration procedures.

A description of Dr. Higgins’ work is provided by the Hair Transplant Forum International:

“After isolating [dermal papilla] from human hair follicles, they grow the human DP cells in spheroid cultures in order to retain their inductive potential. Then they place the dermal papilla spheres between the epidermis and dermis of neonatal foreskin and graft it onto the back of mice. Human [hair follicle] neogenesis can be observed after 6 weeks.”

In essence, the scientists were able to capitalize on the potential of dermal papilla cells to induce the growth of a hair follicle by enclosing the DP cells in a small sphere. When implanted, the DP cells maintained their properties of inducing the development of follicles, and, indeed, follicles did grow.

It is another example of how far our understanding of the biology of hair has come in the last 10 years. And it is another example of scientists closing in on the elusive “hair loss cure.”

Read up on the latest Hair Cloning Research

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Jing Gao, Mindy C. DeRouen, Chih-Hsin Chen, Michael Nguyen, et. al.
Genes & Development 22:2111-2124, 2008

The growth of a hair follicle from its developmental cell stage to a hair bearing follicle is through an interactive process between epidermal cells and those of the dermal papilla. It was found that Laminin-511 is instrumental in facilitating this process.

It has been felt that the extra-cellular protein Laminin is critical to both adhesion and the signaling process in hair development; however, the mechanism is not fully understood.

Through this study, it was shown that the signaling pathways introduced by the administration of noggin and sonic hedgehog alone were insufficient to develop a hair follicle. When Laminin-511 protein was introduced to the tissue culture, the dermal papilla developed. When the protein was inhibited, hair follicle growth again ceased. This information supports prior studies suggesting that Laminin is critical in the early stages of follicle cell development and is required for continued follicle development and growth.

This study reaffirms in vitro and in vivo studies in mice, the importance of Laminin-511 in the formation of dermal papilla to promote the development of more organized dermal papilla cells and the hair follicle development. It also suggests that there is a reciprocal mechanism between the signaling pathways of noggin and sonic hedgehog with Laminin-511.

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Q: Considering cell cultivation is made possible how could their injection create a normal formation of hair on the scalp and can they induce hair growth also in scarred areas where previously hair stopped growing?

A: That is the question. It is not known if these induced follicles will resemble normal hairs, and be cosmetically acceptable on their own, or if they will grow unruly and must be used as a filler behind more aesthetically pleasing transplanted hair.

Hair growth is an interaction between the dermal components (fibroblasts in the dermal sheath and dermal papillae) and the epidermal structures.

It is possible that the injected dermal fibroblasts will interact with resident epithelial cells to produce a properly oriented hair. A tunnel of epithelial cells can also be created to facilitate this process and some researchers are using cultures of both dermal and epithelial cells.

As you suggest, part of the challenge is not just to multiply the hair but to find a way for the hair to grow in its proper orientation. With scar tissue, the task will obviously be much more difficult.

Another issue is that the induced follicles are just that, they are single hair follicles rather than complete follicular units. Because of this they wouldn’t have the cosmetic elegance of one’s own natural hair, unlike that which is possible in follicular unit hair transplantation.

That said, much work still needs to be done and it is not clear at this time what might be the solution.

Read more on the Hair Cloning page on the Bernstein Medical – Center for Hair Restoration website.

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The British government has awarded Intercytex a grant to automate the production of their new hair regeneration therapy. Intercytex is a cell therapy company that develops products to restore and regenerate skin and hair. Intercytex has partnered with a private company, The Automation Partnership (TAP), to develop an automated manufacturing process for their novel hair multiplication treatment.

The hair multiplication product, ICX-TRC, has been submitted as a hair regeneration therapy that uses cells cloned from one’s own scalp. It is intended for the treatment of male pattern baldness (androgenetic alopecia) and female pattern hair loss. The key researcher, biochemist Dr. Paul Kemp, founder of Intercytex, is developing the hair multiplication treatment at their Manchester facility. This investment in hair cloning research is spearheaded by UK Science Minister, Lord Sainsbury.

The government grant will be used mainly to develop a robotic system specifically designed to support the commercial-scale production of their hair cloning product ICX-TRC, at a scale that can handle a large number of people. The company is currently in Phase II clinical testing.

How Intercytex’s Hair Cloning Product Works

Intercytex’s method of hair regeneration involves removing a slice of the scalp, complete with hairs and follicles, from the back of the head. Hair follicles from this area are most resistant to typical hereditary baldness. The sample is taken to a laboratory where the hair producing dermal papilla (DP) cells are extracted and multiplied in flasks. After eight weeks, the DP cells should have cloned into millions of hair cells.

To complete the hair cloning process, the new cells are injected back into the patient’s scalp under a local anesthetic. These cultured cells should then develop into brand new hair follicles.

Intercytex

Intercytex is a 6-year-old company with its main office is in Cambridge, UK and has a clinical production facility and research and development laboratories in Manchester, UK. Additional laboratories are located in Boston, Massachusetts. TAP, founded in 1988, is a private company with headquarters near Cambridge, UK. Intercytex is publicly traded on the London Stock exchange (LSE: ICX).

Additional information about this hair cloning product can be found at www.intercytex.com.

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