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Utilizing Dermal Papilla Cells for Hair and Skin Growth

Abstract
Hair loss is a major problem, with millions of victims worldwide. Ranging from cancer
patients to old men, there are people who want hair but are unable to have it. Current attempts at
solving this problem, including using donor hair follicles and relocating a set number of hairs
from the back of the scalp to the front, have their respective consequences. Therefore, we
propose a new method that is still under development to solve this issue: using lab produced
dermal papilla cells to stimulate hair growth. These cells allow the growth of new hair follicles
using a patients own cells, instead of relying on donors and a set number of cells being
relocated. Dermal papilla cells can also be used to stimulate skin cell regeneration, which can be
used to cure burns and other problems resulting in skin loss. Dermal papilla cells are useful and
essential in solving both of these issues, and can be implemented in the near future.














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Present Technology
Current hair loss treatment methods include taking medicine, undergoing surgery, and
wearing a fake hairpiece. All of these methods have their respective flaws and side effects. The
only two FDA approved medicines are Rogaine, made of Minoxidil, and Propecia, made of
Finasteride. The former, Minoxidil, is an over the counter liquid that one can rub into the scalp,
and it may give hair regrowth or slow down the rate of hair loss. However, it may take 12 weeks
for new hair to begin growing, and it can cause irritation to the scalp and unwanted hair growth
on areas of the skin that were not applied on. In fact, only 10 to 14 percent of people who try it
experience hair growth (WebMD). The latter, Finasteride, is a pill that attempts to treat male hair
loss. Its side effects include reduced sexual drive and function. Furthermore, there is a possibility
of increased chances of prostate cancer for men, as warned by the FDA. No women can use it,
because it is designed to be used by men only. The greatest problem is that when its use is
discontinued, the results will disappear. Both these types of medicine do not give satisfactory
results and they can bring many unwanted outcomes. As one user puts it, Propecia and other
medicines dont work. Dont let the doctors lie to you. Propecia eventually stops working and
your hair loss will continue. Minoxidil is absolutely worthless. (RealSelf)
The surgical methods offered include hair transplants and scalp reduction. Hair
transplants, also called hair grafting, a dermatological surgeon removes a part of the scalp from
the back of the head, which is does bear hair. This section is cut into small segments and then
transplanted onto the area which does not have hair. When done correctly, this can produce a
natural look; however, this can only be obtained after many sessions, and can take many months.
During the process, one can experience swelling, bruising, itching in the area where scalp was
removed, or a lack of sensation in that area. It costs about $40,000, and the return is 25% of the


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scalps original density. As one ages, the cosmetic effects will lessen. The donor area will thin
over time. This is the horrible truth hair transplant doctors dont tell you. (RealSelf)
Another surgical method for dealing with hair loss is scalp reduction. In scalp reduction,
the area of the scalp without hair is removed, and the area with hair is stretched to cover the
removed area. This procedure can be very painful. Headaches are common, and patients will
usually feel tightness around their head. Both hair grafting and scalp reduction can result in large
scars.
All of these surgical methods are expensive and painful. Not everyone can afford them,
and not everyone would want to go through these procedures. On top of this, they take a long
time and have risks and side effects.
Finally, wearing a wig is not a true medical solution, and it does not inherently solve the
problem - people still wish for hair. All of these current methods are unsatisfactory, as they
cannot guarantee success and also bring many negative side effects.

History
The idea of wigs and fake hair pieces have existed for millennia. These devices to give
the illusion of hair have Wigs have existed since around 3000 BCE in societies such as the
Assyrians, Sumerians, Cretans, Carthaginians, Persians, and Greeks. In ancient times, there were
medical prescriptions for hair loss that included the use of herbs, however none were substantial.
Rogaine is made with the drug Minoxidil. Originally, this drug was used to treat high
blood pressure. As people used it, one of its side effects was hair growth. In 1988, Rogaine was
created and first made available. Finasteride was first used in Propecia in 1997, when Merck &
Co. obtained approval from the FDA for using it in treating baldness.


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Modern hair surgery arose in the 1930s. In 1939, Dr. Okuda from Japan published a new
study on restoring hair by surgery for burn victims. His method employed a punch technique
which extracted round sections of skin and transferred them to areas which needed more hair
growth. Dr. Tamura refined this technique in 1943, and it is similar to the current techniques
being used today. The first successful hair transplant in the United States was performed in 1954,
when Dr. Norman Orentreich performed a hair transplant on a man suffering from baldness. Dr.
Orentreich later published his theory of Donor Dominance. The techniques of Dr. Orentreich
and Dr. Okuda were crude, and there were commonly large disasters which made the public stray
away from the poorly reputed surgical method. This changed in the 1990s however, when the
idea of manipulating the follicular unit arose. These surgical methods are the ones that are used
today.
Future Technology
The idea of cloning hair follicles has been around for decades. Scientists already know
that dermal papilla cells, that are found inside the hair follicles, can give rise to new follicles.
However, once the dermal papilla cells are put into conventional, two-dimensional tissue culture,
they revert to basic skin cells and lose their ability to produce hair follicles. So researchers were
faced with a problem: how to expand a sufficiently large number of cells for hair regeneration
while retaining their inductive properties.
To solve this, they decided to use mice. They reasoned that the clumps of rodent skin
papillae were somehow creating their own environment, allowing them to interact and send
signals in a way that reprogrammed the recipient skin to grow new follicles. So they tested their
idea by harvesting dermal papillae from seven human donors and cloned them in tissue culture -
without adding any additional growth factors. After a few days, they transplanted the papillae


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clones, which had formed into three-dimensional "spheroids" in the tissue culture, between the
dermis and epidermis of human skin that had been grafted onto the backs of mice. Five of the
seven transplants generated new hair growth that lasted at least 6 weeks.
The new approach would actually increase the number of hair cells able to produce hair.
It would take fewer hair cells (leaving a much smaller scar), grow them in a lab culture, then
transplant the multiplied cells back into the bald or thinning parts of the patient's scalp. If it leads
to clinical success, the technique could benefit not only men in early stages of baldness, but also
women with hair loss, who are mostly unable to use current transplant treatments because of
insufficient donor hair. Of course, this method has only been tested on rodents so far. The next
step would be applying it to actual hair hair follicles, but more work needs to be done.
Co-lead author Angela M. Christiano, the Richard and Mildred Rhodebeck Professor of
Dermatology and professor of genetics & development at Columbia, explains: "This method
offers the possibility of inducing large numbers of hair follicles or rejuvenating existing hair
follicles, starting with cells grown from just a few hundred donor hairs. It could make hair
transplantation available to individuals with a limited number of follicles, including those with
female-pattern hair loss, scarring alopecia, and hair loss due to burns."
However, the application of dermal papillae cells is not limited to hair follicles. Scientists
are also planning to use this breakthrough in technology and apply it to skin regeneration. They
believe that these cells can be used to effectively treat burns and heal wounds in the future. If this
succeeded, it would be a major achievement in the medical field, and with the current
development of the use of dermal papillae cells reaching great heights, this goal is not far from
reach.


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Breakthroughs
Professor Christiano and colleagues harvested dermal papillae from seven human donors
and cloned the cells in tissue culture, and no additional growth factors were added to the cultures.
After a few days, the cultured papillae were transplanted between the dermis and epidermis of
human skin that had been grafted onto the backs of mice. In five of the seven tests, the
transplants resulted in new hair growth that lasted at least six weeks. (UPI) The success of hair
growth in mice was the first step in proving that dermal papillae cells could eventually be used
for human hair regeneration.
Colin Jahoda, who is also co-director of the North East England Stem Cell Institute,
created clumps. He popped 3,000 papilla cells into drops of cultures on dish lids, then turned the
lids over, so they were hanging. The 3,000 cells moved to the bottom of the drops, as they
apparently do in the scalp. The proximity of the cells to each other, in that particular way,
worked. When papilla cells were taken from seven patients, placed in hanging drops, and then
shot into hairless human foreskin grafted on the backs of mice, new human hair cells grew in five
of seven grafts. This also showed the possibility of creating new hair follicles.
These recent breakthroughs have only involved mice, but they are steps in the right
direction. The potential of dermal papillae is evident, and with more research, this concept will
no doubt see more success.
Design Process
The topic of genes controlling hair growth has been hotly disputed, with no research to
solidly back up any claims of a specific gene that directly controls dermal papilla (DP)
neogenesis, up until now. In the present study Leif Carlsson's research team identifies the
transcription factor Lhx2 as an important regulator of hair formation. The Lhx2 gene is active


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during the hair follicle's growth phase and is turned off during the resting period. The scientists
have been able to show that Lhx2 is functionally involved in the formation of hair, as hair
follicles in which Lhx2 has been inactivated cannot produce hair. Moreover, the activation of the
Lhx2 gene in hair follicles has been shown to activate the growth phase and hence the formation
of hair. Thus, Lhx2 is a gene that is important for the regulation of hair growth.
In stark contrast to previously published research findings from other teams of scientists,
Leif Carlsson and his colleagues found that Lhx2 is primarily expressed outside the so-called
bulge region of the hair follicle, where the follicle's stem cells are found. The Ume researchers
have also shown that Lhx2 is necessary for the hair follicle's growth (anagen) phase to proceed
and for the hair follicle's structuring. Moreover, transgenic expression of Lhx2 after birth is
sufficient to activate the growth phase and stimulate hair growth.
These findings allow for an alternative interpretation of the function of Lhx2 in hair
follicles compared with previous results. Lhx2 is expressed periodically, primarily in precursor
cells that are distinct from the cells in the bulging region of the follicles. It is a factor that is
necessary for hair to be formed and to grow. Our team took gene therapy into consideration as a
viable pathway for DP neogenesis. However, upon further research, the methods behind
regulation of gene expression proved to be far too complex for us to deal with. One of the most
common way of controlling gene expression is the methylation of DNA. DNA is typically
methylated by methyltransferase enzymes on cytosine nucleotides in a CpG dinucleotide
sequence. In order to be able to control the expression of this particular gene, we would have to
manufacture a certain promoter enzyme to specifically attach to the ends of the gene so that
methylation would be able to specifically target that certain gene. We felt that this was too
difficult a task to accomplish in the coming decade. (Sci-News)


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Our team also looked into possible improvements of hair growth shampoos and other
hair products. Out of all the hair products we researched, nearly all of them employed a
dihydrotestosterone (DHT) blocker. DHT is a male sex hormone, an androgen. 5-reductase, an
enzyme, synthesizes DHT in the adrenal glands, hair follicles, testes and prostate. Male and
female adults can lose hair as a consequence of changes in the metabolism of androgen in the
body - men more commonly than women. And to mitigate the effects of DHT, many hair product
companies used one of two drugs in their products, dutasteride or finasteride. The reason why
our team chose not to pursue this path is we found it difficult to build off the current technologies
and innovations of hair products. These drugs are working at their maximum efficiency and there
is little practicality in improving these products in the next decade or two. (MayoClinic)
Another treatment currently being offered to bald or balding people is hair transplants.
Hair transplantation is a surgical technique that moves individual hair follicles from a part of the
body called the 'donor site' to bald or balding part of the body known as the 'recipient site'. In this
minimally invasive procedure, grafts containing hair follicles that are genetically resistant to
balding are transplanted to the bald scalp.The reason it works is because hair is moved from parts
of your head where the follicles aren't sensitive to DHT, thus promoting growth of DHT-resistant
follicles in bald areas. The most common and successful method is strip harvesting. Strip
harvesting is the most common technique for removing hair and follicles from a donor site. The
surgeon harvests a strip of skin from the posterior scalp, in an area of good hair growth. A single-
, double-, or triple-bladed scalpel is used to remove strips of hair-bearing tissue from the donor
site. Each incision is planned so that intact hair follicles are removed. The excised strip is about
11.5 x 1530 cm in size. While closing the resulting wound, assistants begin to dissect
individual follicular unit grafts, which are small, naturally formed groupings of hair follicles,


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from the strip. Working with binocular stereo-microscopes, they carefully remove excess fibrous
and fatty tissue while trying to avoid damage to the follicular cells that will be used for grafting.
The latest method of closure is called 'Trichophytic closure' which results in much finer scars at
the donor area. (WebMD)
The surgeon then uses very small micro blades or fine needles to puncture the sites for
receiving the grafts, placing them in a predetermined density and pattern, and angling the
wounds in a consistent fashion to promote a realistic hair pattern. The technicians generally do
the final part of the procedure, inserting the individual grafts in place.
Strip harvesting will leave a "pencil thin" linear scar in the donor area, which is typically
covered by a patient's hair even at relatively short lengths. The recovery period is around 2
weeks and will require the stitches/staples to be removed by medical personnel or sub cuticular
suturing can be done. Our group chose not to pursue this path either because we found no room
for improvement for an already established and successful, though expensive, treatment.
(WebMD)
All three of the pathways we researched all had one thing in common; they were all
already viable treatments for baldness and had little room for growth and improvement. We
chose to further research the culturing of DP cells because this is something that has yet to be
fully proven effective, and we firmly believe that if it does prove to be effective, it can be applied
in many other cases outside of DP cells.
Consequences
Currently, the effectiveness of reintroducing cultured DP cells has yet to be proven more
effective, if not as effective as current hair loss products and drugs. History tells us that nearly


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any treatment comes with side effects, so if this procedure if applied on say, a cancer patient and
is ineffective and unable to grow hair, not only has the cancer patient not gained anything, but
the patient has also suffered through the possible side effects of going through the treatment.
Since we not only want to be able to perform neogenesis of DP cells, we want to ensure
that our method is 100% viable and is more effective and is more reliable than any other on the
market. One branch of our research is aimed towards providing immediate relief to injured
soldiers in combat by using patches that have cultured skin cells on them. If the patches fail to do
their jobs, not only have we not helped the soldier, we have also wasted valuable time that the
soldier could have spent undergoing a perhaps slower, but surer procedure.
But, if our research proves to be practical, many people who do not appreciate their
baldness can gain a little bit of their happiness back. Cancer patients who lose their hair to
chemotherapy will definitely be comforted by the return of their hair. Though they may not be
winning the fight against their disease, the return of the hair should give them a sense of hope
that will build towards a stronger self confidence. And for people in general who care greatly
about their appearance, our research may prove to be a vital part of these peoples future lives. It
all just depends.










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Diagrams







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Bibliography
1. Baldness cure a step closer with promising new treatment. (2013, October 22). Medical
News Today. Retrieved November 1, 2013, from
http://www.medicalnewstoday.com/articles/
2. Cloning cells may be answer to male and female hair loss. (2013, October 22). UPI.
Retrieved November 2, 2013, from
http://www.upi.com/Health_News/2013/10/22/Cloning-cells-may-be-answer-to-male-
and-female-hair-loss/UPI-28901382486223/#ixzz2jGQFgDsp
3. Grady, D. (2013, October 21). New Technique Holds Promise for Hair Growth.The New
York Times. Retrieved November 2, 2013, from
http://www.nytimes.com/2013/10/22/science/new-technique-holds-promise-for-hair-
loss.html?_r=1&
4. New Method Generates Human Hair Growth from Dermal Papilla Cells. (2013, October
21). Breaking Science News SciNews.com. Retrieved November 2, 2013, from
http://www.sci-news.com/medicine/science-human-hair-dermal-papilla-01480.html
5. Hair Loss Grafting, Transplants, and Other Treatments. (n.d.). WebMD. Retrieved
November 22, 2013, from http://www.webmd.com/skin-problems-and-treatments/hair-
loss/cosmetic-procedures-hair-loss?page=2
6. Staff, Mayo Clinic (2012, March 29). Definition. Mayo Clinic. Retrieved November 22,
2013, from http://www.mayoclinic.com/health/hair-
loss/DS00278/DSECTION=treatments-and-drugs


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7. Hair Loss Grafting, Transplants, and Other Treatments. (n.d.). WebMD. Retrieved
November 22, 2013, from http://www.webmd.com/skin-problems-and-treatments/hair-
loss/cosmetic-procedures-hair-loss?page=2




















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