Hair cloning, Hair Multiplication (HM), Stem Cell Therapy, Genetic Engineering (Gene Therapy)

At the outset it is important to know that cloning as it sounds fascinating is not only clinicallybut even experimentally successful in human beings. There are mainly 2 companies Aderans of America ( Japanese  owned) and the UK based  Intercytex  are into these experiments and world is looking for any positive that comes out from their efforts. Although it appears form recent evidence that it may not be less that 10 years away before it ic available clinically. Following information is compiled to give idea about developing and related topics.

It was known to the scientists that the Embryonic stem cells have pluripotent characteristics i.e. they can develop in to any body tissue given proper environment.

There is a big ethical issue involved in the use of Embryonic Stem cells due to possible loss of life.

 The following experiment made it clear that even some adult tissues cells have Pluripotent characteristics they are called Adult Stem Cells. The significance of Adult stem cells is not having such a potential loss of life.

What is cloning?                                                                                                                                   

Cloning technically means the production of genetically identical organisms. The first clone of animal was Dolly, the famous Edinburgh sheep. Although technically not an exact replica of her mother (and therefore not a true clone), the revolutionary part of the experiment was that it overturned the long-held view that non-sex cells of an adult (somatic cells e.g. of liver, lungs. Brain, skin etc.) were differentiated to such a degree that they lost any potential to develop into a new adult organism or in other words other genes in the cell became permanently inactive. The other major challenge was to be able to initiate the multiplication of the genetically altered cell and then to provide the proper environment in which the growth of the new organism could take place. 

Transgender Induction of Follicles: (1999)

From the idea of producing genetically identical organism it was natural to come to the idea of genetically identical organ or for that sake hair follicle (which is no less than an organ with multiple tissues and complexity of an organ). Earliest successful work done in this field is that of Colon Jahoda of England. In their paper Transgender Induction of hair Follicles,  the researchers have shown that dermal sheath cells (essentially a  fibroblast-  an Adult stem cells) , found in the lower part of the human follicle, was isolated from one person ( a male) and then injected into the fore arm skin of genetically unrelated another person (a female) to promote the formation of new intact hair. The implanted cells interacted locally to stimulate the creation of full terminal (i.e. normal) hair follicles. Although this is not actually cloning the dermal sheath cells can potentially be multiplied in a Petri dish and then injected in great numbers to produce a full head of hair. The word potentially is highlighted, as this multiplication has not yet been accomplished. It seems, however, that this hair “induction” processes is the model most likely to work. It is well known that fibroblasts, unlike many other tissue cells, are relatively easy to culture. Theoretically, a patient's fibroblasts could be removed from the sheaths of just a few follicles and then cultured to produce thousands of follicles. These fibroblasts could then be injected back into the scalp to induce thousands of new hair follicles to grow. So far this important single study has not been reproduced.

Another interesting aspect of their experiment is that the donor cells came from a male but the recipient, who actually grew the hair, was a female. The importance of this is that donor cells can be transferred from one person to another without being rejected. Since repeat implantations did not provoke the typical rejection responses, even though the donor was of the opposite sex and had a significantly different genetic profile, this indicates that the dermal sheath cells have a special immune status and that the lower hair follicle is one of the bodies “immune privileged” sites.

Unlike, Follicular Unit Transplantation (FUT), in which an intact follicular units are planted into the scalp in the exact direction the surgeon wants the hair to grow, with cell implantation there is no guarantee that the induced hair will grow in the right direction or have the color, hair thickness or texture to look natural. However, it is not even certain that the induced follicles will actually grow long enough to produce cosmetically significant hair. And once that hair is shed in the normal hair cycle, there are no assurances that it will grow and cycle again. A major technical problem to cloning hair is that cells in culture (unlike the Cloning of the whole organism in the uterus - a proper environment) begin to de-differentiate as they multiply and revert to acting like fibroblasts again, rather than hair.

In another experiment (2009)

The study — conducted by Marwa Fawzi, a dermatologist at the University of Cairo Faculty of Medicine, and reported on Bloomberg.com — used stem cells from the scalps of eight children with alopecia areata to regenerate their own hair:
The Cairo researcher took small amounts of skin from the scalps of the children, isolated the hair follicle stem cells that stimulate hair production, and grew them in the lab, increasing the number of cells. After one month, she put the cells back into the scalps of the children, with numerous injections across the bald areas of their heads. Six months after the hair cloning treatment, an evaluation showed a 50% increase in hair in more than half of the subjects. Dr. Fawzi took new skin samples and examined the hair follicles themselves and could see that the injected stem cells had migrated into the follicles. There, the stem cells stimulated the follicles to transition from a dormant phase to a hair-generating phase.  (Posted on Bloomberg.com, July 10, 2009)

Adult skin can regenerate new hair follicles. -  2007

In the recent study published in Nature it is repored that in mice large skin wounds can regenerate new hair follicles.Report by Dr. George Cotsarelis, a dermatology professor at the University of Pennsylvania School of Medicine in Philadelphia underlines that in regenerating woulds skin undergoes processes similar to these during embryonic development which results in formation of new hair follicles. This process happens in wounds of adult animals. This fact shows that mammals and humans have better regenerative abilities than commonly believed.

These new findings could provide basis for developing new treatment strategy for male-pattern baldness and other types of hair loss. It is shown that hair follicles newly formed from wounds functioned normally, cycle through the normal stages of hair cycle. More importantly, hair fibers that they produce are indistinguishable from pre-existing hairs with one exception - lack of pigmentation.

Finding details:

In the reported experiments scientists produced relatively large wounds on the backs of adult mice. When wounds reached a certain size new hair follicles developed at the center of wounds. This developmental process closely resembled normal embryonic development of hair follicles.

It appears that as the part of this hair neogenesis non-hair skin stem cells were able to transform into hair cell types. It was shown that the stem cells that gave rise to de novo hair follicles were not stem cells usually associated with hair follicle development (i.e. bulge stem cells). Dr. Cotsarelis comments: "...They're actually coming from epidermal cells that don't normally make hair follicles. So they're somehow reprogrammed and told to make a follicle..."

Dr. Cotsarelis is affiliated with with Follica Inc., that has a license for the patent on this process of hair regeneration from wounds . He predicts that it will be more than 5 years before a baldness treatment will be available.

These experiments have shown that Inducer role of  Fibroblasts of Dermal Papilla, DP (and or Dermal Sheath Cell ,DSC) [DP cells (fibroblasts) can be grown and multiplied in culture so that a small number can produce enough hair follicles to cover an entire bald scalp.] to induce Hair Follicle formation esp. in presence of Pluripotent Progenitor Stem cells -Epithelial cells of Matrix keratinocytes.

 Methods of cloning:

While considerable work remains on turning hair cloning methods into a viable treatment for hair loss, there are four experimental techniques described in a 2008 paper in Hair Transplant Forum International — the primary medical journal in the field of hair transplantation — that shed some light on how cloning could become a viable treatment in hair restoration. * Teumer J. Strategies for follicular cell implantation. Hair Transplant Forum International 2008.

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1. Implant Dermal Papillae Cells Alone

• Implant DP cells into the dermis
• Cause the overlying skin cells (keratinocytes) to be transformed into hair follicles
• Referred to as “Follicular neo-genesis” since new hair is formed on previously bald scalp
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2. Implant Cloned Dermal Papillae Cells Next to Miniaturized Follicles [ a model used by Intercytex for research-called Follicular cell regeneration]

• DP cells induce the keratinocytes of the miniaturized follicles to grow into terminal hairs
• Advantage: existing miniaturized follicles already have the proper structure and orientation to produce a natural look

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3. Implant Dermal Papillae Cells with Keratinocytes (“Proto-Hairs”)-[ A model followed by Aderans company of US- called follicular Neogenesis]

• Keratinocytes and DP cells are cultured together until partial hair formation takes place
• These culture-grown hairs (“proto-hairs”) are implanted in the skin
• Advantage: better hair direction because of the orientation of the proto-hair

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4. Implant Cells Using a Matrix

• DP cells alone or in combination with keratinocytes are placed in a matrix of collagen or synthetic materials
• Matrix acts like a scaffold to help cells organize to form a follicle and direct its growth

Problem is that the cultured cells (or Cloning) :

1. May lose their ability to differentiate into hair follicles with multiple passages

2. Hair direction may be uncontrolled. With mouse experiments, the hairs grow at all different directions instead of in the right direction.

3. Hair, may not be of a quality that is cosmetically acceptable and matches the patient existing hair.

4. And the hair may not grow in follicular units. Individual hairs will not give the fullness or natural look of follicular units.

5. Issue of safety: Are we sure that cultured cells may not turn into something else – such as malignancy cells with uncontrolled growth?

6. Finally, FDA approval would be required and this takes few years time

What is Hair Multiplication? (HM)

HM is a wider term that also includes other methods besides cloning. In hair multiplication, hairs are simply plucked from the scalp or beard and then implanted into the bald part of the scalp. The idea is that some germinative cells at the base of the hair follicle will be pulled out along with the hair. Once the hair is re-implanted, these cells would be able to regenerate a new follicle. In theory, microscopic examination of the plucked hair could help the doctor determine which hairs have the most stem cells attached and thus which are most likely to regrow. The procedure is called “hair multiplication” since the plucked follicles would regrow a new hair, potentially giving an unlimited supply.
In a modification of this procedure, the bulbs of the hair are separated from the shafts and then their cells (matrix keratinocytes and Mesodermal sheath or papilla cells) cultivated in vitro (outside the body). After the cells are multiplied, they are injected into the pores of local, dormant hair follicles in the balding area. The problem with either technique is that matrix keratinocytes (the plucked cells) are only transient amplifiers, and the stem cells around the bulge region of the follicle, the ones most important for hair growth, are not harvested in any significant numbers and can’t be readily activated to produce a hair. 

Genetic Engineering

In contrast to replicating whole organisms, in genetic engineering, one alters the DNA of a particular cell so that it can manufacture proteins to correct genetic defects or produce other beneficial changes in an organism. The initial step in genetic engineering is to isolate the gene that is responsible for the problem. The next step is to clone (multiply) the gene. The last step is to insert the gene inside the cell so that it can work to alter bodily function.
The focus of such work is to identify the defect that causes the problem we wish to fix and then to develop a drug, enzyme blocker, or another approach to address the problem. There are many baby steps taking us to that cure and Dr. Markus M Nothen of the University of Bonn in Germany identified an androgen receptor gene on the ‘X’ Chromosome which is contributed by the mother in setting a person up for balding. The androgen receptor gene helps govern the workings of male sex hormones (androgens), such as testosterone.

Though these hormones promote the growth of body and facial hair, on the scalp excess androgens may cause hair loss. Dr. Nothen believes that this is only one of possibly many genes that trigger the balding process

Some  websites about hair follicle cloning or which follow it closely are…
1. Aderans Research Institute: “dedicated to developing state-of-the-art cell engineering solutions for hair loss.”
2. Intercytex: It promotes “an autologous hair regeneration therapy, a suspension of human dermal papilla (DP) cells, for the treatment of male pattern baldness and female diffuse alopecia.” According to latest news the company has gone bust and has closed down the research operation in January 2010.
3.  Follica:  “Developing novel therapies for conditions and disorders of the hair follicle, the epicenter for the development and replenishment of human hair and skin.”
4.  Histogen:  It is marketing “a proprietary liquid formula created by the culturing of newborn fibroblasts in an embryonic-like environment and then harvesting the naturally secreted growth factors, anitoxidants and other synergistic bioproducts that are produced” that, it claims, may have “significant applications” as “an injectable for hair growth.”
5.  Luna Innovations:  It is use “nanomedicine” to stimulate new hair growth.
6.  Hair Science Institute:  Dr. Coen Gho’s clinic that claims a superior method for individual follicle transplantation.
7.  Phoenix Bio:  A Japanese biotech company that “propagates hair papillar cells which are the key element in hair growth and develops therapies that enable the implantation of these cells on patients thus regenerating the ability of the patient’s scalp to produce hair naturally.”
8.  Shisheido Research:  Another Japanese company that is doing research into hair multiplication technologies.
9.  Bernstein Medical Center for Hair Restoration:  An advanced hair transplantation clinic, the Bernstein Center also follows closely developments in hair cloning technologies and is a good source for a
“hands on” reality check on what is realistic at the moment.
10.Doctors of St Vincent’s Hospital in Melbourne and Melbourne University in Australia with the leadership of Professor Sinclair are also in to stem cell research according to latest report

 Curtersy: Doctorbersnstein's site

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