Bernstein Medical - Center for Hair Restoration - Dr. Angela Christiano

Dr. Angela Christiano

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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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Q: I read, with considerable interest, your excellent article on the latest in Dr. Angela Christiano’s work on follicular neogenesis. It seems to me that the next questions we should be asking are: when will testing begin on human subjects and when might her research develop into a hair cloning treatment that is available to the general public?

A: It is very difficult to determine when this phase of the research might begin and it is even harder to predict when treatment might become available. First, the technology is not quite there. Dr. Christiano showed in her recent paper that changing the environment of skin (fibroblast) cells so that they could form into 3-D cultures enabled them to induce human hair-follicle growth. Although this was a major step towards cloning hair, additional work needs to be done before we will be able to mass produce fully-functioning human hair follicles to the extent needed for hair transplantation.

In addition, research on human subjects requires that experiments meet rigorous federal regulatory standards and these take time to be approved and carried out. Supposing that further study of follicle neogenesis results in a breakthrough treatment for hair loss, this treatment would still require meeting substantial efficacy and safety requirements of the FDA before it would be made available to the public. We will be communicating important developments as they occur through our Hair Cloning Research section and through periodic updates in the Bernstein Medical Newsletter.

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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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Q: There was a retrospective study by Lotufo et al. linking male pattern baldness to heart disease. Do you think there are other links like this for androgenetic alopecia? — J.L., San Francisco, CA

A: Family studies revealed both the androgen receptor locus on the X chromosome, as well as a new locus on chromosome 3q26. Association studies performed in two independent groups revealed a locus on chromosome 20 (not near any known genes) as well as the androgen receptor on the X chromosome.

So far, the genetic studies for androgenetic alopecia (AGA) have not revealed identification of a particular gene other than the androgen receptor, as well as the two candidate regions on chromosomes 3 and 20. Inasmuch as the androgen receptor can be involved in other diseases, this might be a feasible connection. Until candidate genes are identified that underlie AGA, it is impossible to predict where the commonalities might lie.

Excerpted from Angela Christiano, Hair Transplant Forum International 2011; 21(1): 14-15.

Read more about Hair Loss Genetics, and see some other Hair Restoration Answers posts on the topic.

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Dr. Christiano Interviewed on Alopecia, Hair Loss by New York TimesDr. Angela Christiano, a colleague of Dr. Bernstein’s at Columbia University, has been studying the causes of alopecia areata and genetic hair loss for many years. She, in fact, suffers from the disease as well.

The New York Times has published a question and answer interview with Dr. Christiano which covers her own struggle with alopecia, her research into the causes of genetic hair loss, and where she sees the field going in the future. Here is one exchange that offers a window into how her research is breaking new ground in the field of hair loss genetics:

Q. When were you able to actually do the study?

A. In 2008. We published our findings this past July. Ours was the first study of alopecia to use a genome-wide approach. By checking the DNA of 1,000 alopecia patients against a control group of 1,000 without it, we identified 139 markers for the disease across the genome.

We also found a big surprise. For years, people thought that alopecia was probably the stepchild of autoimmune skin diseases like psoriasis and vitiligo. The astonishing news is that it shares virtually no genes with those. It’s actually linked to rheumatoid arthritis, diabetes 1 and celiac disease.

Continued discovery by Dr. Christiano and others in the field of hair loss genetics will lead to clues like these, which will shape the future of hair loss treatment. The hope for hair loss sufferers around the world is that a medical treatment can be developed which will effectively cure androgenetic alopecia, or common baldness. There is a lot of ground to be covered and there are many studies yet to be conducted, but progress is being made.

You can read more about Dr. Christiano’s research on our Hair Loss Genetics News page.

Read the article and listen to a two minute audio stream of the interview at the NYT.

Photo c/o Ruth Fremson/The New York Times

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Dr. Angela Christiano of Columbia University in New York and a team of scientific researchers have identified a new gene involved in hair growth. Their discovery may affect the direction of future research for hair loss and the diagnosis and ultimate prevention of male pattern baldness.

The condition which leads to thinning hair is called hereditary hypotrichosis simplex. Through the study of families in Pakistan and Italy who suffer from this condition, the team was able to identify a mutation of the APCDD1 gene located in chromosome 18. This chromosome has been linked to other causes of hair loss.

According to Dr. Christiano, “The identification of this gene underlying hereditary hypotrichosis simplex has afforded us an opportunity to gain insight into the process of hair follicle miniaturization, which is most commonly observed in male pattern hair loss or androgenetic alopecia.”

The mutation of the APCDD1 gene inhibits the Wnt signaling pathway. Although this recently discovered gene does not explain the complex process of male pattern baldness, the importance of this discovery lies in the Wnt signaling that the gene directs, has now been shown to control hair growth in humans, as well as in mice.

Reference: Nature 464, 1043-1047 (15 April 2010) | doi:10.1038/nature08875;

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