1Utilizing 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 patient’s 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.

2Present 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 don’t work. Don’t 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

3scalp’s 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 don’t 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.

4Modern hair surgery arose in the 1930’s. 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 1990’s 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

5clones, 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.

6Breakthroughs

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

7during 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 Umeå 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)

8Our 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. 5α-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 1–1.5 x 15–30 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,

9from 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

10any 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.

11Diagrams

12Bibliography

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